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  • Structure-based screening and molecular dynamics simulation studies for the identification of potential acetylcholinesterase inhibitors
    Mol. Simulat. (IF 1.782) Pub Date : 2019-10-27
    Ankit Ganeshpurkar; Ravi Singh; Pravin Gangaram Gore; Devendra Kumar; Gopichand Gutti; Ashok Kumar; Sushil Kumar Singh

    Alzheimer’s disease (AD) is an irreversible, progressive neurodegenerative disease characterised by the appearance of amyloid β plaques and neurofibrillary tangles in the brain. The loss of cholinergic neurons is considered to be one of the contributing factors for cognitive and memory deficits in the disease. Donepezil, the most successful and prescribed drug to treat the symptoms of AD, is acetylcholinesterase (AChE) inhibitor that improves the memory and brain’s cognitive functions. In this study, the pharmacophoric features of donepezil were mapped from its cocrystal with AChE and were used to screen the Zinc15 database. The obtained hits were subjected to molecular properties and PAINS filter. The homology modelling and molecular dynamics (MD) were performed to prepare selected AChE protein model (PDB id 4EY7) for advanced studies. The virtual screening and precision docking led to the identification of five compounds. The ADMET property prediction and free energy calculations were carried out to obtain three final compounds. The Alanine scanning and MD study of the compounds viz. ZINC000013719534, ZINC000035551243 and ZINC000035596918 produced stable complexes of the ligands. The identified virtual leads have the potential for better AChE inhibition. Highlights Pharmacophore mapping of donepezil was developed from PDB id 4EY7. Pharmacophore-based screening yielded 601 compounds with RMSD < 0.5 Å. PAINS and Drug likeliness filtration resulted in 199 compounds for further virtual screening and precision docking studies. Free binding energy and ADMET studies provided three active compounds. The molecular dynamics study indicated that the compounds ZINC000013719534, ZINC000035551243 and ZINC000035596918 formed stable interactions with the protein.

    更新日期:2020-01-07
  • DFT simulation of Watson–Crick-like guanine–thymine mismatch in quaternary systems involving DNA bases
    Mol. Simulat. (IF 1.782) Pub Date : 2019-12-06
    Zahra Anvari; Hamid Reza Masoodi; Sotoodeh Bagheri

    The aim of this work is to theoretically investigate the guanine–thymine mismatch in the presence of adenine–thymine and guanine–cytosine base pairs. At M06-2X/6-311++G(d,p) level, the absolute values of formation energy of quaternary systems increase by going from systems having enol form of guanine (G*) to those containing enol tautomer of thymine (T*). Moreover, the stacking between T* and purine bases, in comparison with pyrimidine bases, increases the stability of quaternary systems having T*. On the other hand, the stacking between G* and pyrimidine bases more stabilises systems involving G*. From a thermodynamic point of view, the quaternary systems containing G−T* can transform their geometries into systems having G*−T. To gain a better understanding of the influence of hydrogen bonds on the stability of systems, the atoms in molecules and natural bond orbital analyses are used to evaluate the strength of hydrogen bonds in the investigated systems.

    更新日期:2020-01-07
  • Free energy calculation using space filled design and weighted reconstruction: a modified single sweep approach
    Mol. Simulat. (IF 1.782) Pub Date : 2019-11-18
    Anindya Bhaduri; Jasmine Gardner; Cameron F. Abrams; Lori Graham-Brady

    A modified single sweep approach is proposed for generating free energy landscapes. The approach replaces the use of temperature-accelerated molecular dynamics (TAMD) to generate centres in collective variable (CV) space at which mean forces are computed using restrained molecular dynamics (MD) simulations with a sequential space-filling design. This approach also modifies the radial basis function reconstruction step of the traditional single sweep approach and proposes a weighted reconstruction of the free energy surface using the previously generated mean forces. The modified approach is compared to the traditional single sweep (SS) approach on the (φ, ψ) dihedral free-energy map of solvated alanine dipeptide (AD). It is found that the new approach results in a more accurate reconstructed free energy than does the traditional approach when compared to the directly-computed reference free energy landscape. It is shown that the increased accuracy of the overall map stems from the improved 1-dimensional space filling (projective) property of the proposed design compared to that of the TAMD generated centres. A further enhancement in the accuracy of the crucial lower energy regions is enabled by the introduction of weights in the reconstruction step that give more importance to lower energy-valued regions.

    更新日期:2020-01-07
  • Theoretical study of Schiff bases reactivity prediction of corrosion inhibition effect
    Mol. Simulat. (IF 1.782) Pub Date : 2019-11-14
    Radia Mahboub

    We investigated the reactivity of some para-substitued Schiff bases by performing quantum chemical calculations using the density functional theory method. First, we employed this method to predict reliable orbital molecular energies. Then, we calculated the quantum chemical parameters: energy gap, chemical hardness and Mullikan electronegativity. Our simulated results prove that the presence of intermolecular hydrogen bond increases the gap in HOPySB4 Schiff base and the electrophilicity index increases with electronegativity effect (ClPySB2). So, we deduce that the reactivity and selectivity are generated by its structure. This study establishes that the fraction of electrons for HOPySB4 is large. We have also evaluated the conformations of these molecules using the molecular dynamics simulation in gas and in solution. We conform that the HOPySB4 reaches its high stable conformation state in the solution environment. We compared theses calculated results and conclude that the HOPySB4 Schiff base is an inhibitor of choice. Molecular simulations give us very good results in the prediction of reactivity and inhibition effect.

    更新日期:2020-01-07
  • Feasibility of the multi-particle collision dynamics method as a simulation technique for a magnetic particle suspension
    Mol. Simulat. (IF 1.782) Pub Date : 2019-11-19
    Akira Satoh

    We have elucidated the feasibility of the multi-particle collision dynamics (MPCD) method as a technique for the simulation of a magnetic particle suspension, by addressing the dependence of the translational and rotational Brownian motion of the magnetic particles on the parameters that characterise a MPCD simulation. A reasonable level of activation of the Brownian motion is indispensable for simulating the aggregate structures of the magnetic particles because their internal structure is strongly dependent on particle Brownian motion. In the present study, we have employed a diffuse reflection model for treating the interaction between the fluid and the magnetic particles. The diffuse reflection model gives rise to the tendency that the translational Brownian motion of the magnetic particles is more significantly activated than the rotational Brownian motion. If a scaling coefficient is introduced for modifying the interaction between the fluid and the magnetic particles, a more accurate solution may be obtained in regard to the aggregate structures of the magnetic particles. We may conclude that the MPCD method with the diffuse reflection model is a promising simulation technique for analysing the behaviour of magnetic particles in a suspension.

    更新日期:2020-01-07
  • Wetting of single crystalline and amorphous silicon surfaces: effective range of intermolecular forces for wetting
    Mol. Simulat. (IF 1.782) Pub Date : 2019-11-25
    H. Gokberk Ozcelik; A. Cihan Ozdemir; Bohung Kim; Murat Barisik

    Wetting at nanoscale is a property of a three-dimensional region with a finite length into the solid domain from the surface. Understanding the extent of the solid region effective on wetting is important for recent coating applications as well as for both crystalline and amorphous solids of different atomic ordering. For such a case, we studied the wetting behaviour of silicon surfaces at various crystalline and amorphous states. Molecular distributions of amorphous systems were varied by changing the amorphisation conditions of silicon. Semi-cylindrical water droplets were formed on the surfaces to be large enough to remain independent of line tension and Tolman length effects. Contact angles showed up to 38% variation by the change in the atomic orientation of silicon. Instead of a homogeneous solid density definition, we calculated different solid densities for a given surface measured inside different extents from the interface. We correlated the observed wetting variation with each of these different solid densities to determine which extent governs the wetting variation. We observed that the variation of solid density measured inside a 0.13 nm extent from the surface reflected the variation of wetting angle better for both single crystalline and amorphous silicon surfaces.

    更新日期:2020-01-07
  • Modelling of Ca2+-promoted structural effects in wild type and post-translationally modified Connexin26
    Mol. Simulat. (IF 1.782) Pub Date : 2019-11-27
    Paolo Calligari; Mauro Torsello; Marco Bortoli; Laura Orian; Antonino Polimeno

    Connexins (Cx) are a class of membrane proteins important for auditory function, intercellular signalling and skin biology. Although the presence of concentration of calcium ions is known to work as a trigger for the Cx functionality, the structural changes induced by calcium binding still need to be well elucidated. In this computational study, we have explored the structural effects promoted by Ca2+ on both the wild type (Cx26WT) and on two post-translationally modified Connexin 26 (Cx26): Cx26E42-47γ, which contains two glutamates (E42 and E47) that are γ-carboxylated and Cx26R75m, where a key arginine (R75) is N-monomethylated. These modified amino acids, whose forcefield parameters have been developed in this work, alter Cx26 structure around the Ca2+coordination site. Structural changes were assessed from the analysis of molecular dynamics (MD) simulations. We observed a strict relation between the chemical properties of the post-translational modifications and significantly different responses of Cx26 to Ca2+-binding, while charge-adding modifications have destabilising effects upon calcium coordination, the uncharged ones share the same structural properties of the wild-type counterpart. Overall, these findings suggest the critical role of the electrostatic network flanking the Ca2+ coordination site in maintaining the native tertiary and quaternary structures.

    更新日期:2020-01-07
  • A combined force field for the silica/nickel system
    Mol. Simulat. (IF 1.782) Pub Date : 2019-11-26
    Sergio Damián-Vázquez; Juan F. J. Alvarado; Edgar O. Castrejón-González

    Silica and nickel are frequently used in the synthesis of carbon nanotubes by the chemical vapour deposition (CVD) process. The molecular simulation of this process requires the knowledge of force fields to model the interactions occurring between those species at the atomic scale. This work proposes a combined force field to model the silica/nickel system when these components are in contact as substrate and catalyst, respectively, in the CVD process. The proposed combined force field includes the Lennard–Jones (n–m) potential for modelling the silicon/nickel pair interactions and the Buckingham potential for the oxygen/nickel pair interactions. The combined force field is completed by the Tersoff potential to model silica (SiO2) and the Sutton–Chen potential for the cohesive forces present in the nickel clusters. Parameters for the Lennard–Jones (n–m) and Buckingham pair potentials were fitted, by the least squares technique, to interaction energies data for the silica/nickel system. The energies were obtained from Ab-initio (DFT) calculations using the VASP code. It was found that the combined force field reproduces adequately, by molecular dynamics simulation, the adherence (adsorption) of nickel clusters on the silica surface. Keeping stable this configuration is crucial in modelling the carbon nanotubes synthesis by the CVD process.

    更新日期:2020-01-07
  • Effects of ion–water Lennard-Jones potentials on the hydration dynamics around a monovalent atomic ion in molecular dynamics simulations
    Mol. Simulat. (IF 1.782) Pub Date : 2019-10-11
    Kota Kasahara; Yuki Takimoto; Ryoi Ashida; Takuya Takahashi

    The molecular dynamics (MD) method is a promising technique to dissect the atomistic details of water dynamics around a solute. However, the quantitative predictions of experimentally measured kinetic properties, e.g. translational diffusion coefficient (D) and rotational relaxation time (τ), are not straightforward. Current water models have failed to reproduce these properties quantitatively; therefore, the fine-tuning of water models is required. In this study, we examined the effects of ion–water Lennard-Jones (LJ) potentials on the water dynamics around a monovalent atomic ion. For the TIP5P water model, we introduced new LJ potentials for the ion–hydrogen and ion–pseudoatom interactions, which were zero in the original TIP5P model. The hydration properties, i.e. D, τ, and the radius of the first hydration shell (rMO), were examined for various parameter settings. As a result, the new parameters certainly improved the reproducibility of the hydration properties in correspondence with experimental values. However, it is still difficult to reproduce faster rotational relaxation of hydration water than that of bulk water. In addition, we found that the three hydration properties (D, τ, and rMO) were artificially correlated in the MD simulations.

    更新日期:2019-12-18
  • Influence of micro grooves of diamond tool on silicon cutting: a molecular dynamic study
    Mol. Simulat. (IF 1.782) Pub Date : 2019-10-13
    Changlin Liu; Jianguo Zhang; Junjie Zhang; Xiao Chen; Wenbin He; Junfeng Xiao; Jianfeng Xu

    During single-point diamond turning of hard and brittle materials, tool wear is a dominant factor that influences machinability. In the wear process, micro grooves on the flank face is an important character of tool wear, which leads to the formation of subcutting edges and the ductile to brittle transition. In this paper, classical molecular dynamic simulations of nanometric cutting of silicon by a diamond tool with V-shape grooves were carried out to explore the effect of groove geometry on the workpiece and tool integrity. The evolution of tool wear and machined surface integrity was discussed. Simulation result shows that grooves have a significant influence on the stress and temperature distributions of the tool, which has a great influence on tool deterioration. Grooves with sharp edges will lead to severe tool wear and bring deep subsurface damage of the machined surface. However, the subsurface damage of the machined surface can be restrained with blunt grooves since the pressure is reduced. With a comprehensive understanding and controlling of groove, tool wear can be suppressed and high-quality surface can be achieved.

    更新日期:2019-12-18
  • Square-well mixtures revisited: computer simulation, mixing rules and one-fluid theory
    Mol. Simulat. (IF 1.782) Pub Date : 2019-10-16
    B. P. Akhouri; J. R. Solana

    Extensive Monte Carlo simulations have been performed to obtain the thermodynamic properties of binary square-well mixtures for different compositions, well depths, hard-core diameter ratios and temperatures. They are used in combination with a one-fluid theory based on perturbation theory to analyse the performance of several mixing rules proposed in the literature. A new density- and temperature-dependent mixing rule is proposed. The new mixing rule provides better agreement with simulations than those previously proposed, especially for very asymmetric mixtures.

    更新日期:2019-12-18
  • Molecular dynamics simulation study of Glycine tip-functionalisation of single-walled carbon nanotubes as emerging nanovectors for the delivery of anticancer drugs
    Mol. Simulat. (IF 1.782) Pub Date : 2019-10-31
    Zahra Ghadri; Heidar Raissi; Mahnaz Shahabi; Farzaneh Farzad

    In this work, molecular dynamics (MD) simulations have been performed to explore dynamic properties of three anticancer drugs including Exemestane (EXE), Letrozole (LTZ) and Fulvestrant (FLV) interacting with single-walled carbon nanotubes (SWCNTs) as drug delivery systems in a biological environment. Furthermore, the effect of functionalisation of SWCNTs with Glycine (Gly) group on the drug adsorption process is investigated. The MD simulation results show that among three investigated drugs, FLV with high hydrophobic characteristic exhibits the strongest affinity for hydrophobic SWCNT (16, 8) in terms of the binding free (ΔGbin) amount energy. Moreover, strong binding of FLV drug molecules on the functionalised single-walled carbon nanotube (f-SWCNT) with (16, 0) chirality is facilitated by more active sites available for hydrogen bond (HB) formation between drug molecules and the functional groups of SWCNT. Because of more number of HBs in the simulation system, there are more numbers of hydrophilic interactions between the adsorbed drug molecules and the functional groups of the nanotube.

    更新日期:2019-12-18
  • A molecular dynamics study of crosslinked epoxy networks: construction of atomistic models
    Mol. Simulat. (IF 1.782) Pub Date : 2019-10-20
    Yaguang Sun; Yafang Guo; Hua Yang

    In this paper, molecular dynamics (MD) simulations are used to construct atomistic models of crosslinked epoxy networks. An improved algorithm, which considers both the cutoff distance criterion and the orientation criterion, has been developed to construct the realistic, well-equilibrated crosslinked epoxy networks. Epoxy networks containing diglycidyl ether bisphenol-A (DGEBA) as epoxy resin and tricarballylic acid as crosslinking agent are obtained using this algorithm. The results show that this algorithm can effectively decrease the molecular configurations that have unrealistic newly formed bond angles. Some important properties such as glass transition temperature (Tg), coefficient of thermal expansion (CTE) and Young’s modulus are calculated from the equilibrated structures, which are in good agreement with existing experimental and simulated results.

    更新日期:2019-12-18
  • Theoretical study of the effect of π-linkers on triarylamine-based p-type D-π-A sensitiser
    Mol. Simulat. (IF 1.782) Pub Date : 2019-10-22
    Li-Xiao Kong; Chang-Shan Zhang; Qi-Ying Xia; Xue-Hai Ju

    Six p-type dyes with D-π-A structures were designed, and their molecular structures and electronic properties were studied by the density functional theory and the time-dependent density functional theory. Thiophene, thiophene[3,4-c][1,2,5] thiadiazide and thiazole[5,4-d]thiazole in combination with dithieno[3,2-b:2',3'-d]thiophene (s-DTT) were introduced into the newly designed dyes to extend π-linkers. The results showed that the enhanced conjugation of π-linkers increases the coplanarity and decreases HOMO–LUMO gap of the dyes. The absorption spectra of dyes 1–6 are obviously red-shifted. Compared to those of QT-1, the spectra of dyes 3 and 6 are red-shifted by 128 and 154 nm, and the oscillator strengths are improved by 70% and 71%, respectively. Dyes 3 and 6 have not only the strongest absorption peaks, but also a large absorption area in the range of 400–900 nm. This guarantees them stronger light absorptions. They also have the maximum charge separation degree (t), resulting a reduced hole recombination. Furthermore, the light harvesting efficiency (LHE), hole injection power (ΔGinj), dye renewable power (ΔGreg) and charge recombination force (ΔGCR) of dyes 3 and 6 are superior to those of other dyes. In addition, the bromine substitution can effectively promote the red-shift of the absorption spectra.

    更新日期:2019-12-18
  • A review on the mechanical and thermal properties of graphene and graphene-based polymer nanocomposites: understanding of modelling and MD simulation
    Mol. Simulat. (IF 1.782) Pub Date : 2019-10-20
    Amit Kumar; Kamal Sharma; Amit Rai Dixit

    Simulation of molecular dynamics (MD) allows mimicking the systematic variation of mechanical properties beyond the capacity of experimental methods. In this review, the status of the molecular modelling, simulation and mechanical and thermal characterisation of graphene and the properties of bulk nanocomposites using MD are extensively examined. The molecular models of graphene (pristine and functionalised), and the most common epoxy matrix with preeminent MD energy minimisation tools are thoroughly examined. The presence of MD’s simulation setup and the computational procedure for different styles of mixing the polymer matrix with graphene as nanofiller are exhaustively reviewed. In particular, in the analysis of several papers on graphene and their composites, it has been noticed that mechanical, thermal and interfacial properties are ubiquitous to most of the engineering applications. In this review, advances in the molecular modelling and simulation of graphene and their composites has been discussed in detail keeping graphene structures, aspect ratio, weight fraction and density effect as major factors. Finally, the research gaps and future scope are discussed, which indeed helps the researchers in scaling up their researches in graphene and their composites, which may further lead to their experimental findings.

    更新日期:2019-12-18
  • Theoretical investigation on the interaction mechanism of FOX-7/AP mixed crystals
    Mol. Simulat. (IF 1.782) Pub Date : 2019-10-31
    Jun Tao; Xiaofeng Wang

    Herein, in order to determine the formation feasibility of 1,1-diamino-2,2-dinitroethylene (FOX-7)/ ammonium perchlorate (AP) mixed crystals, three configurations of FOX-7/AP composites (FOX-7/AP1, FOX-7/AP2, FOX-7/AP3) were optimised, and the structures of FOX-7/AP mixed crystals were constructed. Then the electrostatic potential, binding energy and electronic density topology of FOX-7/AP composites were calculated by using the density functional theory. Finally, the radial distribution function between H atoms and O atoms of FOX-7/AP mixtures was calculated through molecular dynamics. As demonstrated by the results, there are hydrogen bond interactions in three configurations of FOX-7/AP composites. The interaction energies of FOX-7/AP1, FOX-7/AP2 and FOX-7/AP3 are 8.396, 20.537 and 38.189 kJ▪mol−1, respectively. The order of the electron density ρ(r) at the bond critical point (BCP) of three FOX-7/AP composites is FOX7-AP3 > FOX7-AP2 > FOX7-AP1. There are apparent peaks at the range of 0.11–0.31 nm and 0.31–0.5 nm for FOX-7(10-1)/AP, FOX-7(011)/AP, FOX-7(101)/AP mixed crystals. The interaction strength of the hydrogen bond is greater than that of strong van der Waals force. Therefore, it is feasible to combine FOX-7 with AP to form mixed crystals. As the content of AP in the mixed crystal is on the rise, the oxygen balance of the system shows a gradually increasing trend.

    更新日期:2019-12-18
  • On using the anisotropy in the thermal resistance of solid–fluid interfaces to more effectively cool nano-electronics
    Mol. Simulat. (IF 1.782) Pub Date : 2019-11-06
    Xiaoyu Wang; David Venerus; Ishwar K. Puri; Sohail Murad

    As power-intensive electronic components are further miniaturised into nanodevices, their heat dissipation is a serious operational and safety concern. While nanochannels and nanofins are often used for facilitating heat dissipation, the liquid-solid interfaces that form (Kapitza resistance), become significant barriers to heat transfer. We demonstrate that the thermal resistance of these interfaces is strongly anisotropic. The resistance of an interface to heat transfer parallel to the interface (solid surface) is significantly smaller than the more well-known Kapitza resistance (associated with heat transfer across the interface – perpendicular to the solid surface) and is even lower than that of the bulk fluid. As a result, if devices are designed to dissipate heat parallel to an interface, heat dissipation can be significantly enhanced. Our studies are also able to explain the molecular basis of this observed anisotropy in interfacial resistance, which has hitherto remained unreported for solid–liquid interfaces.

    更新日期:2019-12-18
  • Molecular docking and simulation analysis for elucidation of toxic effects of dicyclohexyl phthalate (DCHP) in glucocorticoid receptor-mediated adipogenesis
    Mol. Simulat. (IF 1.782) Pub Date : 2019-09-02
    Neha Singh, Vikram Dalal, Pravindra Kumar

    ‘Obesogens’ are chemical agents that improperly regulate the genes involved in glucose metabolism and adipocyte differentiation and promote lipid accumulation and adipogenesis. The human glucocorticoid receptor (hGR) is a steroid hormone triggered transcriptional factor and regulates target genes important in basal glucose homeostasis. Molecular docking analysis was performed in order to assess in-silico structure based toxic effects of high molecular weight phthalates dicyclohexyl phthalate (DCHP) and its monophthalate metabolite mono-cyclohexyl phthalate (MCHP). Molecular docking results show that the binding affinities of DCHP and MCHP lie in the comparable range (−7.87 kcal/mol and −6.24 kcal/mol) with Dexamethasone (−10.2 kcal/mol), a potent agonist for hGR. These two PAEs occupy the active site of hGR and interact with the key residues. Molecular simulation results infer that hGR-PAEs complexes were stable. Density functional theory (DFT) analysis indicates that HOMO and LUMO energy gap of DCHP (3.88 eV) and MCHP (3.39 eV) are comparable to DEX (4.69 eV). Binding free energy calculations of the DCHP-hGR and MCHP-hGR complexes were estimated by using Molecular Mechanic/Poisson-Boltzmann Surface Area (MMPBSA) method. Molecular Docking and simulation results emphasise that DCHP and MCHP can efficiently bind to hGR, which further leads to glucocorticoid-mediated adipogenesis in a synergistic manner.

    更新日期:2019-12-02
  • Aromatic versus aliphatic thiols on Au(111) surface: a DFT exploration of adsorption registry and electronic structure
    Mol. Simulat. (IF 1.782) Pub Date : 2019-09-10
    Yeliz Gurdal

    Self-assembled monolayers (SAMs) on metal surfaces have inspired many interesting applications, such as chemical and biological sensors, molecular electronics, magnetism and protective coatings. In this respect, SAMs having different head and tail groups have been synthesised which allow the modification of the material properties by tuning intermolecular, monolayer–metal and/or monolayer–solvent interactions. In this respect, we investigate the adsorption of thiols having aromatic, p-mercaptobenzonitrile (pPhCN) or aliphatic, 2-azidoethanthiol (N3S), tail groups on Au(111) surface by means of Density Functional Theory (DFT). Monomer and dimer adsorption configurations of both pPhCN and N3S molecules as well as the modification of the electronic structures upon adsorption are studied. Our results show that different adsorption mechanisms are observed for the molecules under consideration. While monomer and dimer structures of the pPhCN prefer to adsorb laterally on the surface, for N3S vertical arrangement of the molecules enhances the molecular immobilisation. Although, dominant contributions to the adsorption energy of the laterally adsorbed pPhCN are through S–Au chemical bond, phenyl ring–surface and cyano N–surface interactions, π–π stacking of the rings contributes to the stabilisation of the complex in addition to the S–Au chemical bond in the case of vertical attachment. For N3S, on the other hand, only S–Au chemical bond determines the adsorption strength. S–Au interactions result in broad molecular orbital redistribution of the S atoms of both molecules, due to the rehybridisation of S and Au states. Density of cyano-N and cyano-C states present in the pPhCN is affected by the orientation of the rings with respect to each other. In the case of 2N3S, instead, the distribution of the tail group molecular orbitals is not modified by the adsorption.

    更新日期:2019-12-02
  • Directed transport of liquid droplets on vibrating substrates with asymmetric corrugations and patterned wettability: a dissipative particle dynamics study
    Mol. Simulat. (IF 1.782) Pub Date : 2019-09-20
    Xinran Geng, Xiaopeng Yu, Luyao Bao, Nikolai V. Priezjev, Yang Lu

    The development of digital (droplet-based) microfluidic (DMF) devices has received significant attention due to their importance for chemical and biomedical analyses. The precise control and manipulation of liquid droplets on a solid substrate is a major requirement for DMF devices. In this study, we propose a novel strategy to generate continuous droplet motion by combining asymmetric corrugations and patterned wettability on a vibrating substrate. The time periodic oscillations of the substrate with asymmetric triangle corrugations provide the input energy to transport a droplet along patterned stripes. Using dissipative particle dynamic (DPD) simulations, we demonstrate that hydrophobic stripes on a superhydrophobic substrate create a wettability step, which effectively constrains the droplet motion along the stripe. Due to the special design of asymmetric triangle corrugations and orientation of hydrophobic stripes, the proposed strategy enables the transport of multiple droplets with different initial locations towards a single spot and coalescence into a large droplet. We further identify a power-law dependence between the droplet velocity and the period of substrate vibration and show that this function is independent of the droplet size. The proposed droplet transportation strategy can be potentially useful for the efficient manipulation of liquid droplets in DMF devices.

    更新日期:2019-12-02
  • Exploring the effect of mono- and di-fluorinated triphenylamine-based molecules as electron donors for dye-sensitised solar cells
    Mol. Simulat. (IF 1.782) Pub Date : 2019-09-25
    Ohoud S. Al-Qurashi, Nuha A. Wazzan, I. B. Obot

    Dye that is consisting of donor-π-π-linkers-acceptor (D-π-π-A) is characterised by enhancement of light-harvesting capability in dye-sensitised solar cell (DSSC) applications. In this work, the DFT and TDDFT using the CAM-B3LYP XC-functional with 6-31G+(d) basis set and were used to study the geometrical, electronic, and photovoltaic properties of four dyes. Two of the investigated dyes are previously reported as successful photosensitisers with power conversion efficiencies of 8.22 and 7.0%, and two are novel designed ones. The investigated dyes are based on triphenylamine (TPA) as electron-donor and cyanoacrylic acid (CA) as electron-acceptor groups, and two π-linkers, i.e. dihydrothieno-dioxine (DHO) and fluorophenylene (FP). The four dyes are different in the FP unit which has Fluorine (F) atom/s in different position and with a different number. The study aims to: (1) justify the reported superiority performance of T2FC (with one F atom at the ortho-position with respect to the CA unit) over the T3FC (with one F atom at the meta-position), and (2) explore the effect of incorporating another F atom at the second ortho-position (T26FC) or at the meta-position (T35FC). The results are supported by the data obtained from calculations of adsorption parameters of dyes adsorbed on (TiO2)24 anatase (1 0 1).

    更新日期:2019-12-02
  • Theoretical insights into sensing of hexavalent chromium on buckled and planar polymeric carbon nitride nanosheets of heptazine and triazine structures
    Mol. Simulat. (IF 1.782) Pub Date : 2019-10-07
    Mohammad Ghashghaee, Mehdi Ghambarian, Zahra Azizi

    The applicability of four surface models of graphitic carbon nitride (planar and corrugated nanosheets of triazine and heptazine structures) to detect hexavalent chromium from contaminated environments was investigated theoretically. The sensing was most favourable on hollow sites but with different coordination numbers and geometrical configurations. A substantial variation in the gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) of the 2D material (e.g. from 4.12 to 0.36 eV in the case of buckled heptazine structure) delineated the high capability of the sensor toward the detection of the chromium ion. Remarkable charge transfers (4.466–4.558 e) from the sensor to the analyte were evident from the topological analysis. Neglecting the surface corrugation could overestimate the adsorption energy while underestimating the HOMO–LUMO gap of both types of graphitic carbon nitride. The localised orbital locator (LOL) profiles revealed the ionic nature of the interactions.

    更新日期:2019-12-02
  • Molecular dynamics and DFT study on the structure and dynamics of N-terminal domain HIV-1 capsid inhibitors
    Mol. Simulat. (IF 1.782) Pub Date : 2019-10-10
    Collins U. Ibeji

    HIV-1 infection is a major threat in the world and has drawn much attention. The emergence of drug-resistance to most of the HIV-1 inhibitors has led to the crucial call for new inhibitors that can interact with the amino terminal domain of HIV-1 CAPSID (CA) and disrupt viral replication. In this study, molecular dynamics simulation was performed on two class of 4,5-dihydro-1H-pyrrolo[3,4-c]pyrazol-6 one (pyrrolopyrazolone) HIV-1 inhibitors (BI-1 and BI-2) reported to inhibit early postentry stages of viral replication. The effect of N-methylation on the binding of BI-1 and BI-2 to N-terminal HIV-1 capsid of the enzyme was also studied and the structural features such as root mean square deviation (RMSD), root mean square fluctuation (RMSF), the radius of gyration (Rg) were analysed. Density functional theory (DFT) calculations using M06/6311++G(2d,2p) was employed to further investigate the nature of charge transfer of inhibitors based on the second-order perturbation theory. Results obtained showed that N-methylation enhanced the binding of BI-1 with MMPBSA binding energy of −6.2 kcal mol−1 compared to −4.2 kcal mol−1 of BI-1. N-methylation did not have a considerable effect on the binding energy of BI-2, but the MMPBSA binding energy (BI-2_N-methyl) is better, compared to BI-1 and its N-methylated analogue (BI-1_N-methyl). The MMPBSA energies were consistent with the experimental findings.

    更新日期:2019-12-02
  • Molecular dynamics simulation of a lignite structure simplified model absorbing water
    Mol. Simulat. (IF 1.782) Pub Date : 2019-10-22
    Zherui Chen, Hongxin Qiu, Zhixin Hong, Guanghui Wang

    To study the formation mechanism of hydration films, a lignite molecular model based on FTIR analysis was established. Both the positive and negative extreme values (±184.76 kJ/mol) of the electrostatic potential appear around oxygen-containing functional groups. Water molecules are mainly adsorbed near oxygen-containing functional groups. This paper studies the absorption of lignite for water molecules using MD simulation. With the addition of water molecules, the number of polar groups increases, and the electrostatic potential level of the system increases, causing an increase in the number of active sites. When the amount of water is inadequate for covering the surface of lignite, water molecules adsorb at active sites and places with lower z values. As the number of water molecules increase, the average length of hydrogen bonds between water molecules and that between lignite and water are close to the set values (1.97 and 1.8 Å, respectively). The short-range order structure of the interface has little effect on the average bond length of water molecules, but it reduces the average bond angle by 1°~2°. After a hydration film forms, the increase to the thickness of the hydration film is primarily attributed to hydrogen-bond interaction between water molecules.

    更新日期:2019-12-02
  • Static and dynamic properties of mid-size liquid n- alkanes, C12∼C400: a molecular dynamics simulation study
    Mol. Simulat. (IF 1.782) Pub Date : 2019-08-14
    Song Hi Lee

    In this paper, we have extended our previous study of the static and dynamic properties (self-diffusion coefficient Dself and friction coefficient ζ) of liquid n-alkane systems up C400 at several temperatures (∼2300 K) using molecular dynamics (MD) simulations in the canonical ensembles. For the small n-alkanes with n ≤ 120 (n: the chain length), the chains are clearly ⟨R2 ee⟩/6⟨R2 g⟩ ≥ 1 (1.06 ∼ 1.44), which leads to the conclusion that the liquid n-alkanes are far away from the ideal chain regime. But for the n-alkanes of n ≥ 160, the chains are ⟨R2 ee⟩/6⟨R2 g⟩ ≈ 1, indicating that they are Gaussian. It is found that the long chains of these n-alkanes at high temperatures show abnormalities in density and friction coefficient. We observed a clear transition in the power law dependence of n-alkane self-diffusion coefficient on the molecular weight (M) of n-alkane, Dself ∼ M−γ, occurs in the range C120∼C160 at temperatures of 318, and 618 K, corresponding to a crossover from the ‘oligomer’ to the ‘Rouse’ regime. The entanglement lengths (Ne) are calculated by the Z1 code and discussed shortly.

    更新日期:2019-11-30
  • Single-crystal Al–Cu50Zr50 metallic glass cold welds: tensile and creep behaviour
    Mol. Simulat. (IF 1.782) Pub Date : 2019-09-04
    Rohit Singh, Pradeep Gupta, Natraj Yedla

    Tensile and creep properties of dissimilar cold weld joints (Al (metal)–Cu50Zr50 (metallic glass)) are investigated using molecular dynamics simulations. Embedded atom method potential is used to model the interactions between Al–Cu–Zr atoms. Cold welding is carried out at three different velocities (20, 30 and 40 m/s) and for three interferences (0.4, 1.3 and 2.3 nm). The strength of the welded joints is measured using the tensile test carried out at a strain rate of 1.5 × 109/s. Structure studies by radial distribution function analysis indicate amorphisation of Al in the weld regions. Tensile studies show that the maximum strength is obtained in the sample that is welded for 1.3 nm interference. Creep studies carried out over range of stresses (200–350 MPa) and temperatures (200–500 K) show very short primary creep and significant steady-state creep. The stress exponent n has two values; at lower stress, n = 1.2, and at higher stress, n = 4.06, respectively. The deformation mechanisms are observed to be slip by Shockley partial dislocation and by twinning in Al region. The icosahedral cluster population in metallic glass decreases as the temperature increases and contributes to large plastic strain.

    更新日期:2019-11-30
  • Molecular dynamics study on perfect and defective graphene/calcium-silicate-hydrate composites under tensile loading
    Mol. Simulat. (IF 1.782) Pub Date : 2019-09-06
    Xiaoxuan Guo, Hao Xin, Jian Li, Zhihua Wang, Zhiqiang Li

    Atomic models of graphene/calcium-silicate-hydrate (G/C-S-H) are constructed by embedding perfect or defective graphene in molecular structures of amorphous C-S-H. Molecular dynamics (MD) simulation is utilised to study mechanical properties of the G/C-S-H and the enhancing effect of perfect and defective graphene is compared. The effects of temperature and strain rate on perfect and defective G/C-S-H are also investigated and compared. The results from present simulations show that (i) the defective graphene has better enhancing effect in C-S-H than perfect one and it grows with the increase of defect sizes; (ii) the tensile strength of G/C-S-H decreases with the increase of temperature and the defective G/C-S-H is more susceptible to temperature than the perfect one; (iii) the ultimate strength and the failure strain increase significantly with the increase of strain rate and the effects of strain rate on perfect and defective G/C-S-H are similar. These findings provide important atomic insights for understanding the mechanical behaviours of G/C-S-H composite.

    更新日期:2019-11-04
  • Dissipative particle dynamics simulation of the soft micro actuator using polymer chain displacement in electro-osmotic flow
    Mol. Simulat. (IF 1.782) Pub Date : 2019-08-08
    Ramin Zakeri

    In this research, the numerical simulation of a soft polymer micro actuator performance has been investigated using the dissipative particle dynamics method in electro-osmotic flow. Effective factors including electro-osmotic flow and polymer chain parameters have been studied. First of all, considering a wide range of electro-osmotic parameters, the validation of analytical results is carried out in a simple micro channel. The electric field and zeta potential changes are linearly related to the flow rate, and the kh parameter behaves nonlinearly to around the kh = 10. In the following, a convergent–divergent channel is used for the soft micro actuator simulation in which a polymer chain as a heart of actuation is embedded in the middle. As the main control parameter, the direction of the electric field is changed every 4 s, and it leads to a reciprocating motion. The numerical results indicate that the displacement of the soft polymer chain will be increased by enhancing the electric field, the number of beads, decreasing the harmonic bond coefficient and also exposing more length of a polymer chain in front of fluid flow. The results of this study may be useful for some future applications such as artificial fibres and muscles.

    更新日期:2019-11-04
  • Anticorrosion mechanism of Cr-doped nickel-base alloy in Br/O environment: a DFT study
    Mol. Simulat. (IF 1.782) Pub Date : 2019-08-30
    Jiyong Li, Junqiao Zhao, Hongyun Shao, Yunzhi Zhang, Hao Dong, Lingran Xia, Songqing Hu

    Density functional theory was used to investigate the anticorrosion mechanism of Cr-doped nickel-base alloy in Br/O environment. The adsorption properties including adsorption energy, bond length and electron structure of Br/O on Ni and Cr-doped Ni surfaces have been investigated. We find that the O atom has bigger adsorption activity than the Br atom. The oxide film can be preferentially formed on the Cr-doped nickel-base alloy surface under the coexistence of Br and O atoms. By exploring the interactions between Br and NiO (111) or Cr2O3 (100) surfaces, we demonstrate that oxide films could prevent Br from erosion. Results indicate that Cr2O3 has stronger corrosion resistance than NiO. The corrosion resistance mechanism of Cr-doped nickel-base alloy is summarised into two processes, i.e. competitive adsorption and adsorption inhibition.

    更新日期:2019-11-04
  • Decoding the signature of molecular mechanism involved in mutation associated resistance to 1, 3-benzothiazin-4-ones (Btzs) based DprE1 inhibitors using BTZ043 as a reference drug
    Mol. Simulat. (IF 1.782) Pub Date : 2019-08-29
    Himanshu Verma, Shalki Choudhary, Pankaj Kumar Singh, Aanchal Kashyap, Om Silakari

    Different resistant strains of M. tuberculosis (Mtb) highlight the urgent need of novel anti-tubercular drugs. In mycobacteria, decaprenyl-phosphoryl-β-D-ribose 2’-oxidase (DprE1) is an appealing enzyme to target as it is involved in the biosynthesis of cell wall component arabinogalactan.1, 3-benzothiazin-4-ones (BTZs) based drugs are promising irreversible inhibitors of DprE1. However, a single point mutation of Cys387Ser in DprE1 results in the development of resistance to these drugs. Herein, we made an effort to decode the molecular mechanism of Cys387Ser DprE1 mutation associated resistance in Mtb against BTZs using different in silico techniques. Since the 3D crystal structure of mutant Cys387Ser protein is not yet been solved, thus the homology model was also developed using 4P8N as a template protein with 99.8% homology with the target protein. The computational results suggested that the factors like HOMO–LUMO energy gap, Burgi-Dunitz angle and distance support the covalent inhibition of wild DprE1 by 1, 3-benzothiazin-4-ones class of drugs, using BTZ043 as a reference drug and the same factors support the cause of resistance in case of Cys387Ser mutation. On the basis of these results, it was concluded that BTZ043 can efficiently inhibit the wild type DprE1 than mutant DprE1.

    更新日期:2019-11-04
  • Structural properties of sH hydrate: a DFT study of anisotropy and equation of state
    Mol. Simulat. (IF 1.782) Pub Date : 2019-08-29
    Shaden M. Daghash, Phillip Servio, Alejandro D. Rey

    Structure-H (sH) hydrate is one of the canonical gas hydrates with significant potential applications and scarce characterised material properties despite the wide knowledge available on other gas hydrates. In this work we characterise some of the important physical properties of this hydrate at the atomistic level using Density Functional Theory. Two exchange-correlation functionals (revPBE and DRSLL) were used to simulate six sH hydrate systems encapsulating neohexane and different help gas molecules. The important role of dispersion forces is quantified. The density and isothermal bulk modulus of sH hydrate are higher when dispersion interactions are considered. The presence of those interactions imposes a direct relationship between the hydrate density and its bulk modulus, while their absence reveals the bulk modulus dependency on hydrogen bond density. Anisotropy is a distinguishing feature of this hydrate in distinction to nearly isotropic sI and sII hydrates. Structure-H hydrate experiences a compressional anisotropy in which the a-lattice and the c-lattice constants respond differently to applied pressure showing less compressibility along the c-axis. This compressional anisotropy was found dependant on the chemistry of help gas molecules. Taken together, these property characterisation results and analysis are a significant and novel contribution to the material physics of sH hydrates.

    更新日期:2019-11-04
  • Molecular mechanics and quantum chemical calculations unveil the combating effect of baicalein on human islet amyloid polypeptide aggregates
    Mol. Simulat. (IF 1.782) Pub Date : 2019-08-30
    E. Srinivasan, S. Ravikumar, S. Venkataramanan, Rituraj Purohit, R. Rajasekaran

    Formation of insoluble toxic aggregates by hIAPP polypeptide is found to be a core component for disease pathogenicity of patients suffering from type II diabetes. Naturally occurring polyphenols that possess anti-aggregation property are being majorly studied in the current scenario for treating various conformational diseases. Herein, we study the disaggregation mechanism of naturally occurring polyphenol baicalein, obtained from the roots of S. baicalensis and Indian trumpet flower on hIAPP dimer using quantum chemical calculation and discrete molecular dynamics. Our study reported that a drastic loss in the secondary structural propensity of hIAPP was seen upon binding of baicalein. Notably, the hydrophobic core and the phenolic groups present in the ends of baicalein molecule play a key role in inhibiting the aggregates formed upon binding to the amyloidogenic core region of hIAPP. Thus, our study provides a comprehensive understanding over the disaggregation effect of baicalein on hIAPP dimer from a computational point of view and thereby bridging the gap for future therapeutic strategy in designing the anti-aggregation compounds that inhibit hIAPP amyloids.

    更新日期:2019-11-04
  • Rutin as promising drug for the treatment of Parkinson’s disease: an assessment of MAO-B inhibitory potential by docking, molecular dynamics and DFT studies
    Mol. Simulat. (IF 1.782) Pub Date : 2019-09-06
    Faizul Azam, Honiwa Suliman Abodabos, Ismail M. Taban, Abdalla R. Rfieda, Danish Mahmood, Md Jamir Anwar, Shamshir Khan, Natalia Sizochenko, Giulio Poli, Tiziano Tuccinardi, Hamed I. Ali

    Inhibitors of monoamine oxidase (MAO)-B have been used for many years in the therapy of Parkinson’s disease (PD). Owing to the safety concerns of the currently used agents, the discovery of novel scaffolds is of considerable interest. MAO-B inhibitory potential of rutin, a flavonoid derived from natural sources, has been established in experimental findings. Hence, the current study seeks to examine the interactions between rutin and crystal structure of human MAO-B enzyme. Molecular docking calculations, as well as molecular dynamics simulations, were employed to investigate the binding mode and the stability of the rutin/MAO-B complex. Energies of highest occupied/lowest unoccupied molecular orbitals were computed through DFT studies and used to calculate electron affinity, hardness, chemical potential, electronegativity, and electrophilicity index in order to investigate the capability of these parameters to influence the ligand–receptor interactions. It was found that rutin traverses both the entrance cavity and the substrate cavity, forcing the Ile-199 ‘gate’ to rotate into its open conformation. It results in the fusion of the two cavities of the MAO-B binding site and directly leads to better binding interactions. Results of the current study can be used for lead modification and development of novel drugs for the treatment of PD.

    更新日期:2019-11-04
  • Correction
    Mol. Simulat. (IF 1.782) Pub Date : 2019-08-30

    (2019). Correction. Molecular Simulation: Vol. 45, No. 18, pp. I-I.

    更新日期:2019-11-04
  • The role of molecular modelling and simulation in the discovery and deployment of metal-organic frameworks for gas storage and separation.
    Mol. Simulat. (IF 1.782) Pub Date : 2019-10-04
    Arni Sturluson,Melanie T Huynh,Alec R Kaija,Caleb Laird,Sunghyun Yoon,Feier Hou,Zhenxing Feng,Christopher E Wilmer,Yamil J Colón,Yongchul G Chung,Daniel W Siderius,Cory M Simon

    Metal-organic frameworks (MOFs) are highly tuneable, extended-network, crystalline, nanoporous materials with applications in gas storage, separations, and sensing. We review how molecular models and simulations of gas adsorption in MOFs have informed the discovery of performant MOFs for methane, hydrogen, and oxygen storage, xenon, carbon dioxide, and chemical warfare agent capture, and xylene enrichment. Particularly, we highlight how large, open databases of MOF crystal structures, post-processed to enable molecular simulations, are a platform for computational materials discovery. We discuss how to orient research efforts to routinise the computational discovery of MOFs for adsorption-based engineering applications.

    更新日期:2019-11-01
  • Transition from exo- to endo- Cu absorption in CuSi(n) clusters: A Genetic Algorithms Density Functional Theory (DFT) Study.
    Mol. Simulat. (IF 1.782) Pub Date : 2011-07-26
    Ofelia B Oña,Marta B Ferraro,Julio C Facelli

    The characterization and prediction of the structures of metal silicon clusters is important for nanotechnology research because these clusters can be used as building blocks for nano devices, integrated circuits and solar cells. Several authors have postulated that there is a transition between exo to endo absorption of Cu in Si(n) clusters and showed that for n larger than 9 it is possible to find endohedral clusters. Unfortunately, no global searchers have confirmed this observation, which is based on local optimizations of plausible structures. Here we use parallel Genetic Algorithms (GA), as implemented in our MGAC software, directly coupled with DFT energy calculations to show that the global search of CuSi(n) cluster structures does not find endohedral clusters for n < 8 but finds them for n ≥ 10.

    更新日期:2019-11-01
  • Modelling water with simple Mercedes-Benz models.
    Mol. Simulat. (IF 1.782) Pub Date : 2019-06-04
    Tomaz Urbic

    The structures and properties of biomolecules like proteins, nucleic acids, and membranes depend on water. Water is also very important in industry. Overall, water is unusual substance with more than 70 anomalous properties. The understanding of water is advancing significantly due to theoretical and computational modeling. There are different kind of models, models with fine-scale properties and increasing structural detail with increasing computational expense and simple models which focus on global properties of water like thermodynamics, phase diagram and are less computational expensive. Simplified models give a better understanding of water in ways that complement more complex models. Here, we review a simple model, the two dimensional Mercedes-Benz (MB) model of water. We present results by Monte Carlo simulations for anomalies and phase diagram and application of various theoretical methods.

    更新日期:2019-11-01
  • On the convergence of multi-scale free energy simulations.
    Mol. Simulat. (IF 1.782) Pub Date : 2018-12-26
    Gerhard König,Bernard R Brooks,Walter Thiel,Darrin M York

    In this work we employ simple model systems to evaluate the relative performance of two of the most important free energy methods: The Zwanzig equation (also known as "Free energy perturbation") and Bennett's acceptance ratio method (BAR). Although our examples should be transferable to other kinds of free energy simulations, we focus on applications of multi-scale free energy simulations. Such calculations are especially complex, since they connect two different levels of theory with very different requirements in terms of speed, accuracy, sampling and parallelizability. We try to reconcile all those different factors by developing some simple criteria to guide the early stages of the development of a free energy protocol. This is accomplished by quantifying how many λ intermediate steps and how many potential energy evaluations are necessary in order to reach a certain level of convergence.

    更新日期:2019-11-01
  • Extension of the GLYCAM06 Biomolecular Force Field to Lipids, Lipid Bilayers and Glycolipids.
    Mol. Simulat. (IF 1.782) Pub Date : 2008-01-01
    Matthew B Tessier,Mari L Demarco,Austin B Yongye,Robert J Woods

    GLYCAM06 is a generalisable biomolecular force field that is extendible to diverse molecular classes in the spirit of a small-molecule force field. Here we report parameters for lipids, lipid bilayers and glycolipids for use with GLYCAM06. Only three lipid-specific atom types have been introduced, in keeping with the general philosophy of transferable parameter development. Bond stretching, angle bending, and torsional force constants were derived by fitting to quantum mechanical data for a collection of minimal molecular fragments and related small molecules. Partial atomic charges were computed by fitting to ensemble-averaged quantum-computed molecular electrostatic potentials.In addition to reproducing quantum mechanical internal rotational energies and experimental valence geometries for an array of small molecules, condensed-phase simulations employing the new parameters are shown to reproduce the bulk physical properties of a DMPC lipid bilayer. The new parameters allow for molecular dynamics simulations of complex systems containing lipids, lipid bilayers, glycolipids, and carbohydrates, using an internally consistent force field. By combining the AMBER parameters for proteins with the GLYCAM06 parameters, it is also possible to simulate protein-lipid complexes and proteins in biologically relevant membrane-like environments.

    更新日期:2019-11-01
  • Relative free energy of binding between antimicrobial peptides and SDS or DPC micelles.
    Mol. Simulat. (IF 1.782) Pub Date : 2009-09-01
    Abdallah Sayyed-Ahmad,Himanshu Khandelia,Yiannis N Kaznessis

    We present relative binding free energy calculations for six antimicrobial peptide-micelle systems, three peptides interacting with two types of micelles. The peptides are the scorpion derived antimicrobial peptide (AMP), IsCT and two of its analogues. The micelles are dodecylphosphatidylcholine (DPC) and sodium dodecylsulphate (SDS) micelles. The interfacial electrostatic properties of DPC and SDS micelles are assumed to be similar to those of zwitterionic mammalian and anionic bacterial membrane interfaces, respectively. We test the hypothesis that the binding strength between peptides and the anionic micelle SDS can provide information on peptide antimicrobial activity, since it is widely accepted that AMPs function by binding to and disrupting the predominantly anionic lipid bilayer of the bacterial cytoplasmic membrane. We also test the hypothesis that the binding strength between peptides and the zwitterionic micelle DPC can provide information on peptide haemolytic activities, since it is accepted that they also bind to and disrupt the zwitterionic membrane of mammalian cells. Equilibrium structures of the peptides, micelles and peptide-micelle complexes are obtained from more than 300 ns of molecular dynamics simulations. A thermodynamic cycle is introduced to compute the binding free energy from electrostatic, non-electrostatic and entropic contributions. We find relative binding free energy strengths between peptides and SDS to correlate with the experimentally measured rankings for peptide antimicrobial activities, and relative free energy binding strengths between peptides and DPC to correlate with the observed rankings for peptide haemolytic toxicities. These findings point to the importance of peptide-membrane binding strength for antimicrobial activity and haemolytic activity.

    更新日期:2019-11-01
  • Molecular dynamics simulations of three protegrin-type antimicrobial peptides: interplay between charges at the termini, β-sheet structure and amphiphilic interactions.
    Mol. Simulat. (IF 1.782) Pub Date : 2007-08-01
    D S Bolintineanu,A A Langham,H T Davis,Y N Kaznessis

    We have carried out molecular dynamics simulations of the naturally occurring protegrin PG-1 peptide and two of its mutants, PC-9 and PC-13 in the presence of a dodecyl-phosphocholine (DPC) micelle. The effects of mutations that disrupt the β-sheet structure in the case of PC-9 and reduce the charge at the C-terminus in the case of PC-13 are analyzed. It is found that the surface-bound conformations of the peptides are severely affected by both mutations. PG-1 exhibits a conformation in which the C-terminus and the β-hairpin turn interact strongly with the micelle lipid head groups, while its N-terminal strand bends away from the micelle and resides in the aqueous region; PC-13 exhibits strong interactions with the micelle at its N-terminus as well as the β-hairpin turn region, while retaining a much more compact conformation than PG-1; PC-9 achieves a highly distorted conformation relative to the homologous PG-1 structure, which allows both its termini and the β-hairpin region to interact with the micelle. These significant differences observed as a result of seemingly minor mutations to the sequences of the three peptides are explained in terms of the interplay between residue charges, structural rigidity and amphiphilic interactions. Conservative inferences are made bridging these biophysical interactions and the pharmacological profiles of the peptides.

    更新日期:2019-11-01
  • Conformational Analysis of Stiff Chiral Polymers with End-Constraints.
    Mol. Simulat. (IF 1.782) Pub Date : 2006-01-01
    Jin Seob Kim,Gregory S Chirikjian

    We present a Lie-group-theoretic method for the kinematic and dynamic analysis of chiral semi-flexible polymers with end constraints. The first is to determine the minimum energy conformations of semi-flexible polymers with end constraints, and the second is to perform normal mode analysis based on the determined minimum energy conformations. In this paper, we use concepts from the theory of Lie groups and principles of variational calculus to model such polymers as inextensible or extensible chiral elastic rods with coupling between twisting and bending stiffnesses, and/or between twisting and extension stiffnesses. This method is general enough to include any stiffness and chirality parameters in the context of elastic filament models with the quadratic elastic potential energy function. As an application of this formulation, the analysis of DNA conformations is discussed. We demonstrate our method with examples of DNA conformations in which topological properties such as writhe, twist, and linking number are calculated from the results of the proposed method. Given these minimum energy conformations, we describe how to perform the normal mode analysis. The results presented here build both on recent experimental work in which DNA mechanical properties have been measured, and theoretical work in which the mechanics of non-chiral elastic rods has been studied.

    更新日期:2019-11-01
  • Effects of active site mutations in haemoglobin I from Lucina pectinata: a molecular dynamic study.
    Mol. Simulat. (IF 1.782) Pub Date : 2009-03-21
    Eunice Ramirez,Anthony Cruz,Diana Rodriguez,Lilen Uchima,Ruth Pietri,Alberto Santana,Juan López-Garriga,Gustavo E López

    Haemoglobin I from Lucina pectinata is a monomeric protein consisting of 142 amino acids. Its active site contains a peculiar arrangement of phenylalanine residues (PheB10, PheCD1 and PheE11) and a distal Gln at position E7. Active site mutations at positions B10, E7 and E11 were performed in deoxy haemoglobin I (HbI), followed by 10 ns molecular dynamic simulations. The results showed that the mutations induced changes in domains far from the active site producing more flexible structures than the native HbI. Distance analyses revealed that the heme pocket amino acids at positions E7 and B10 are extremely sensitive to any heme pocket residue mutation. The high flexibility observed by the E7 position suggests an important role in the ligand binding kinetics in ferrous HbI, while both positions play a major role in the ligand stabilisation processes. Furthermore, our results showed that E11Phe plays a pivotal role in protein stability.

    更新日期:2019-11-01
  • Fast multipole methods for particle dynamics.
    Mol. Simulat. (IF 1.782) Pub Date : 2006-01-01
    J Kurzak,B M Pettitt

    The growth of simulations of particle systems has been aided by advances in computer speed and algorithms. The adoption of O(N) algorithms to solve N-body simulation problems has been less rapid due to the fact that such scaling was only competitive for relatively large N. Our work seeks to find algorithmic modifications and practical implementations for intermediate values of N in typical use for molecular simulations. This article reviews fast multipole techniques for calculation of electrostatic interactions in molecular systems. The basic mathematics behind fast summations applied to long ranged forces is presented along with advanced techniques for accelerating the solution, including our most recent developments. The computational efficiency of the new methods facilitates both simulations of large systems as well as longer and therefore more realistic simulations of smaller systems.

    更新日期:2019-11-01
  • Evaluating the stability of disulfide bridges in proteins: a torsional potential energy surface for diethyl disulfide.
    Mol. Simulat. (IF 1.782) Pub Date : 2007-05-01
    N L Haworth,J E Gready,R A George,M A Wouters

    Disulfide bonds formed by the oxidation of cysteine residues in proteins are the major form of intra- and inter-molecular covalent linkages in the polypeptide chain. To better understand the conformational energetics of this linkage, we have used the MP2(full)/6-31G(d) method to generate a full potential energy surface (PES) for the torsion of the model compound diethyl disulfide (DEDS) around its three critical dihedral angles (χ2, χ3, χ2'). The use of ten degree increments for each of the parameters resulted in a continuous, fine-grained surface. This allowed us to accurately predict the relative stabilities of disulfide bonds in high resolution structures from the Protein Data Bank. The MP2(full) surface showed significant qualitative differences from the PES calculated using the Amber force field. In particular, a different ordering was seen for the relative energies of the local minima. Thus, Amber energies are not reliable for comparison of the relative stabilities of disulfide bonds. Surprisingly, the surface did not show a minimum associated with χ2 ∼ - 60°, χ3 ∼ 90, χ2' ∼ - 60°. This is due to steric interference between Hα atoms. Despite this, significant populations of disulfides were found to adopt this conformation. In most cases this conformation is associated with an unusual secondary structure motif, the cross-strand disulfide. The relative instability of cross-strand disulfides is of great interest, as they have the potential to act as functional switches in redox processes.

    更新日期:2019-11-01
  • Internal and environmental effects on folding and dimerization of the Alzheimer's β amyloid peptide.
    Mol. Simulat. (IF 1.782) Pub Date : 2011-05-01
    Priya Anand,Ulrich H E Hansmann

    Amyloid deposits are a hallmark of many diseases. In the case of Alzheimer's disease a turn between 21Ala and 30Ala, stabilized by a salt bridge between 22Glu/23Asp and 28Lys, may nucleate folding and aggregation of the Aβ peptide. In the present paper we test this hypothesis by studying how salt bridge and turn formation vary with intrinsic and environmental changes, and how these changes effect folding and aggregation of the Aβ peptide.

    更新日期:2019-11-01
  • Coarse-Grained Molecular Models of Water: A Review.
    Mol. Simulat. (IF 1.782) Pub Date : 2012-08-21
    Kevin R Hadley,Clare McCabe

    Coarse-grained (CG) models have proven to be very effective tools in the study of phenomena or systems that involve large time- and length-scales. By decreasing the degrees of freedom in the system and using softer interactions than seen in atomistic models, larger timesteps can be used and much longer simulation times can be studied. CG simulations are widely used to study systems of biological importance that are beyond the reach of atomistic simulation, necessitating a computationally efficient and accurate CG model for water. In this review, we discuss the methods used for developing CG water models and the relative advantages and disadvantages of the resulting models. In general, CG water models differ with regards to how many waters each CG group or bead represents, whether analytical or tabular potentials have been used to describe the interactions, and how the model incorporates electrostatic interactions. Finally, how the models are parameterized depends on their application, so, while some are fitted to experimental properties such as surface tension and density, others are fitted to radial distribution functions extracted from atomistic simulations.

    更新日期:2019-11-01
  • QM/MM free energy simulations: recent progress and challenges.
    Mol. Simulat. (IF 1.782) Pub Date : 2016-08-27
    Xiya Lu,Dong Fang,Shingo Ito,Yuko Okamoto,Victor Ovchinnikov,Qiang Cui

    Due to the higher computational cost relative to pure molecular mechanical (MM) simulations, hybrid quantum mechanical/molecular mechanical (QM/MM) free energy simulations particularly require a careful consideration of balancing computational cost and accuracy. Here we review several recent developments in free energy methods most relevant to QM/MM simulations and discuss several topics motivated by these developments using simple but informative examples that involve processes in water. For chemical reactions, we highlight the value of invoking enhanced sampling technique (e.g., replica-exchange) in umbrella sampling calculations and the value of including collective environmental variables (e.g., hydration level) in metadynamics simulations; we also illustrate the sensitivity of string calculations, especially free energy along the path, to various parameters in the computation. Alchemical free energy simulations with a specific thermodynamic cycle are used to probe the effect of including the first solvation shell into the QM region when computing solvation free energies. For cases where high-level QM/MM potential functions are needed, we analyze two different approaches: the QM/MM-MFEP method of Yang and co-workers and perturbative correction to low-level QM/MM free energy results. For the examples analyzed here, both approaches seem productive although care needs to be exercised when analyzing the perturbative corrections.

    更新日期:2019-11-01
  • Unconstrained Enhanced Sampling for Free Energy Calculations of Biomolecules: A Review.
    Mol. Simulat. (IF 1.782) Pub Date : 2016-07-28
    Yinglong Miao,J Andrew McCammon

    Free energy calculations are central to understanding the structure, dynamics and function of biomolecules. Yet insufficient sampling of biomolecular configurations is often regarded as one of the main sources of error. Many enhanced sampling techniques have been developed to address this issue. Notably, enhanced sampling methods based on biasing collective variables (CVs), including the widely used umbrella sampling, adaptive biasing force and metadynamics, have been discussed in a recent excellent review (Abrams and Bussi, Entropy, 2014). Here, we aim to review enhanced sampling methods that do not require predefined system-dependent CVs for biomolecular simulations and as such do not suffer from the hidden energy barrier problem as encountered in the CV-biasing methods. These methods include, but are not limited to, replica exchange/parallel tempering, self-guided molecular/Langevin dynamics, essential energy space random walk and accelerated molecular dynamics. While it is overwhelming to describe all details of each method, we provide a summary of the methods along with the applications and offer our perspectives. We conclude with challenges and prospects of the unconstrained enhanced sampling methods for accurate biomolecular free energy calculations.

    更新日期:2019-11-01
  • Accelerating the weighted histogram analysis method by direct inversion in the iterative subspace.
    Mol. Simulat. (IF 1.782) Pub Date : 2016-07-28
    Cheng Zhang,Chun-Liang Lai,B Montgomery Pettitt

    The weighted histogram analysis method (WHAM) for free energy calculations is a valuable tool to produce free energy differences with the minimal errors. Given multiple simulations, WHAM obtains from the distribution overlaps the optimal statistical estimator of the density of states, from which the free energy differences can be computed. The WHAM equations are often solved by an iterative procedure. In this work, we use a well-known linear algebra algorithm which allows for more rapid convergence to the solution. We find that the computational complexity of the iterative solution to WHAM and the closely-related multiple Bennett acceptance ratio (MBAR) method can be improved by using the method of direct inversion in the iterative subspace. We give examples from a lattice model, a simple liquid and an aqueous protein solution.

    更新日期:2019-11-01
  • To Keep or Not to Keep? The Question of Crystallographic Waters for Enzyme Simulations in Organic Solvent.
    Mol. Simulat. (IF 1.782) Pub Date : 2016-07-13
    Jayangika N Dahanayake,Devaki N Gautam,Rajni Verma,Katie R Mitchell-Koch

    The use of enzymes in non-aqueous solvents expands the use of biocatalysts to hydrophobic substrates, with the ability to tune selectivity of reactions through solvent selection. Non-aqueous enzymology also allows for fundamental studies on the role of water and other solvents in enzyme structure, dynamics, and function. Molecular dynamics simulations serve as a powerful tool in this area, providing detailed atomic information about the effect of solvents on enzyme properties. However, a common protocol for non-aqueous enzyme simulations does not exist. If you want to simulate enzymes in non-aqueous solutions, how many and which crystallographic waters do you keep? In the present work, this question is addressed by determining which crystallographic water molecules lead most quickly to an equilibrated protein structure. Five different methods of selecting and keeping crystallographic waters are used in order to discover which crystallographic waters lead the protein structure to reach an equilibrated structure more rapidly in organic solutions. It is found that buried waters contribute most to rapid equilibration in organic solvent, with slow-diffusing waters giving similar results.

    更新日期:2019-11-01
  • Recent development and application of constant pH molecular dynamics.
    Mol. Simulat. (IF 1.782) Pub Date : 2014-10-14
    Wei Chen,Brian H Morrow,Chuanyin Shi,Jana K Shen

    Solution pH is a critical environmental factor for chemical and biological processes. Over the last decade, significant efforts have been made in the development of constant pH molecular dynamics (pHMD) techniques for gaining detailed insights into pH-coupled dynamical phenomena. In this article we review the advancement of this field in the past five years, placing a special emphasis on the development of the all-atom continuous pHMD technique. We discuss various applications, including the prediction of pKa shifts for proteins, nucleic acids and surfactant assemblies, elucidation of pH-dependent population shifts, protein-protein and protein-RNA binding, as well as the mechanisms of pH-dependent self-assembly and phase transitions of surfactants and peptides. We also discuss future directions for the further improvement of the pHMD techniques.

    更新日期:2019-11-01
  • Recent Developments in Molecular Simulation Approaches to Study Spherical Virus Capsids.
    Mol. Simulat. (IF 1.782) Pub Date : 2014-09-10
    Eric R May

    Viruses are a particularly challenging systems to study via molecular simulation methods. Virus capsids typically consist of over 100 subunit proteins and reach dimensions of over 100 nm; solvated viruses capsid systems can be over 1 million atoms in size. In this review, I will present recent developments which have attempted to overcome the significant computational expense to perform simulations which can inform experimental studies, make useful predictions about biological phenomena and calculate material properties relevant to nanotechnology design efforts.

    更新日期:2019-11-01
  • Recent developments in methods for identifying reaction coordinates.
    Mol. Simulat. (IF 1.782) Pub Date : 2014-09-10
    Wenjin Li,Ao Ma

    In the study of rare events in complex systems with many degrees of freedom, a key element is to identify the reaction coordinates of a given process. Over recent years, a number of methods and protocols have been developed to extract the reaction coordinates based on limited information from molecular dynamics simulations. In this review, we provide a brief survey over a number of major methods developed in the past decade, some of which are discussed in greater detail, to provide an overview of the problems that are partially solved and challenges that still remain. A particular emphasis has been placed on methods for identifying reaction coordinates that are related to the committor.

    更新日期:2019-11-01
  • Overview of simulation studies on the enzymatic activity and conformational dynamics of the GTPase Ras.
    Mol. Simulat. (IF 1.782) Pub Date : 2014-01-01
    Priyanka Prakash,Alemayehu A Gorfe

    Over the last 40 years, we have learnt a great deal about the Ras onco-proteins. These intracellular molecular switches are essential for the function of a variety of physiological processes, including signal transduction cascades responsible for cell growth and proliferation. Molecular simulations and free energy calculations have played an essential role in elucidating the conformational dynamics and energetics underlying the GTP hydrolysis reaction catalysed by Ras. Here we present an overview of the main lessons from molecular simulations on the GTPase reaction and conformational dynamics of this important anti-cancer drug target. In the first part, we summarise insights from quantum mechanical and combined quantum mechanical/molecular mechanical simulations as well as other free energy methods and highlight consensus viewpoints as well as remaining controversies. The second part provides a very brief overview of new insights emerging from large-scale molecular dynamics simulations. We conclude with a perspective regarding future studies of Ras where computational approaches will likely play an active role.

    更新日期:2019-11-01
  • Novel procedure for thermal equilibration in molecular dynamics simulation.
    Mol. Simulat. (IF 1.782) Pub Date : 2009-04-01
    Marco T Gallo,Barry J Grant,Miguel L Teodoro,Julia Melton,Piotr Cieplak,George N Phillips,Boguslaw Stec

    We describe a simple novel procedure for achieving thermal equilibration between a protein and a surrounding solvent during molecular dynamics (MD) simulation. The method uniquely defines the length of simulation time required to achieve thermal equilibrium over a broad range of parameters, thus removing ambiguities associated with the traditional heuristic approaches. The proposed protocol saves simulation time and avoids bias introduced by the inclusion of non-equilibrium events. The key element of the procedure involves coupling only the solvent atoms to a standard heat bath. Measuring progress towards thermal equilibration involves simply monitoring the difference in temperature between the solvent and the protein. Here, we report that the results of MD simulations using the above procedure are measurably improved relative to the traditional approaches in terms of root-mean-square deviations and principal components analysis both indicating significantly less undesirable divergence.

    更新日期:2019-11-01
  • Pentameric Ligand-gated Ion Channels : Insights from Computation.
    Mol. Simulat. (IF 1.782) Pub Date : 2015-05-02
    Reza Salari,Sruthi Murlidaran,Grace Brannigan

    Pentameric ligand-gated ion channels (pLGICs) conduct upon the binding of an agonist and are fundamental to neurotransmission. New insights into the complex mechanisms underlying pLGIC gating, ion selectivity, and modulation have recently been gained via a series of crystal structures in prokaryotes and C .elegans, as well as computational studies relying on these structures. Here we review contributions from a variety of computational approaches, including normal mode analysis, automated docking, and fully atomistic molecular dynamics simulation. Examples from our own research, particularly concerning interactions with general anesthetics and lipids, are used to illustrate predictive results complementary to crystallographic studies.

    更新日期:2019-11-01
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