To greatly expand the druggable genome, fast and accurate predictions of cryptic sites for small molecules binding in target proteins are in high demand. In this study, we have developed a fast and simple conformational sampling scheme guided by normal modes solved from the coarse‐grained elastic models followed by atomistic backbone refinement and side‐chain repacking. Despite the observations of

A novel severe acute respiratory syndrome (SARS)‐like coronavirus (SARS‐CoV‐2) has emerged as a human pathogen, causing global pandemic and resulting in over 400 000 deaths worldwide. The surface spike protein of SARS‐CoV‐2 mediates the process of coronavirus entry into human cells by binding angiotensin‐converting enzyme 2 (ACE2). Due to the critical role in viral‐host interaction and the exposure

Predicting the structure of multi‐protein complexes is a grand challenge in biochemistry, with major implications for basic science and drug discovery. Computational structure prediction methods generally leverage pre‐defined structural features to distinguish accurate structural models from less accurate ones. This raises the question of whether it is possible to learn characteristics of accurate

Azoreductases are being extensively investigated for their ability to initiate degradation of recalcitrant azo dyes through reduction of azo bonds. There is great interest in studying their diversity, structure and function to facilitate better understanding and effective application. Current study reports azoreductase enzyme from Bacillus velezensis, which showed 69.5% identity to the Bacillus subtilis

Granulins (GRN 1‐7) are short (~6 kDa), cysteine‐rich proteins that are generated upon the proteolytic processing of progranulin (PGRN). These peptides, along with their precursor, have been implicated in multiple pathophysiological roles, especially in neurodegenerative diseases. Previously we showed that GRN‐3 and GRN‐5 are fully disordered in the reduced form implicating redox sensitive attributes

The FastDesign protocol in the molecular modeling program Rosetta iterates between sequence optimization and structure refinement to stabilize de novo designed protein structures and complexes. FastDesign has been used previously to design novel protein folds and assemblies with important applications in research and medicine. To promote sampling of alternative conformations and sequences, FastDesign

Cobaltochelatase in aerobic cobalamin biosynthesis is a complex composed of three subunits. The large subunit CobN is a 140‐kDa protein and is homologous to the ChlH subunit of magnesium chelatase. Previously we have reported the 2.5‐Å structure of a cyanobacterial ChlH. Here we present the 1.8‐Å structure of CobN from Mycobacterium tuberculosis. The overall structure of CobN and ChlH is similar, but

Sarcolipin (SLN) is an important transmembrane (TM) protein encoded by long noncoding RNA (lncRNA). SLN is expressed in the sarcoplasmic reticulum (SR) and regulates cardiac and skeletal muscle contractions. SLN forms a pentameric hydrophobic ligand‐gated ion channel. The protonation of Glu7 (protonated SLN, pSLN) and mutation of Thr18 to Ala18 (T18A) have been reported to exert a significant influence

This airticle combines the principal component analysis with persistent homology for applications in biomolecular data analysis. We extend the technique of persistent homology to localized weighted persistent homology to fit the properties of molecules. We introduce this novel PCA in the study of the folding process of residues 1‐28 of amyloid beta peptide in solution. We are able to determine 7 metastable

Coronaviruses are responsible for several epidemics, including the 2002 SARS, 2012 MERS, and COVID‐19. The emergence of recent COVID‐19 pandemic due to SARS‐CoV‐2 virus in December 2019 has resulted in considerable research efforts to design antiviral drugs and other therapeutics against coronaviruses. In this context, it is crucial to understand the biophysical and structural features of the major

We report the crystal structure of PYCH_01220, a hypothetical protein in Pyrococcus yayanosii CH1. This protein is composed of two domains, named Domain A and Domain B. While Domain B is not significantly homologous to known protein structures, Domain A is structurally analogous to the C‐terminal ribonuclease domain of Escherichia coli colicin D. Domain A has a positively charged surface patch rendered

Species in the genus Macaca typically live in multimale‐multifemale social groups with male macaques exhibiting some of the largest testis: body weight ratios among primates. Males are believed to experience intense levels of sperm competition. Several spermatogenesis genes are located on the Y‐chromosome and, interestingly, occasional hybridization between two species has led to the introgression

The present study examined the structure and dynamics of the most active and thermostable carbonic anhydrase, SazCA, probed using molecular dynamics simulations. The molecular system was described by widely used biological force‐fields (AMBER, CHARMM22, CHARMM36, and OPLS‐AA) in conjunction with TIP3P water model. The comparison of molecular dynamics simulation results suggested AMBER to be a suitable

Protein‐protein interactions are critical to protein function, but three‐dimensional (3D) arrangements of interacting proteins have proven hard to predict, even given the identities and 3D structures of the interacting partners. Specifically, identifying the relevant pairwise interaction surfaces remains difficult, often relying on shape complementarity with molecular docking while accounting for molecular

Predicting the range of substrates accepted by an enzyme from its amino acid sequence is challenging. Although sequence‐ and structure‐based annotation approaches are often accurate for predicting broad categories of substrate specificity, they generally cannot predict which specific molecules will be accepted as substrates for a given enzyme, particularly within a class of closely related molecules

The Protein Data Bank (PDB) file format remains a popular format used and supported by many software to represent coordinates of macromolecular structures. It however suffers from drawbacks such as error‐prone manual editing. Because of that, various software toolkits have been developed to facilitate its editing and manipulation, but, to date, there is no online tool available for this purpose. Here

The phylum cyanobacteria are one of the most ancient groups of organisms on the planet and are well recognized due to its wide distribution, ecological role, and biotechnological potential. Cyanobacterial lectins are being extensively explored due to their antiviral activity, mainly because of their capacity of inhibiting HIV strains from infecting human cells by gp120 and gp41 binding. Cianovirin‐N

Allostery governing two conformational states is one of the proposed mechanisms for catch‐bond behavior in adhesive proteins. In FimH, a catch‐bond protein expressed by pathogenic bacteria, separation of two domains disrupts inhibition by the pilin domain. Thus, tensile force can induce a conformational change in the lectin domain, from an inactive state to an active state with high affinity. To better

It is known that a hyperthermostable protein tolerable at temperatures over 100°C can be designed from a soluble globular protein by introducing mutations. To expand the applicability of this technology to membrane proteins, here we report a further thermo‐stabilization of the thermophilic rhodopsin from Thermus thermophilus JL‐18 as a model membrane protein. Ten single mutations in the extramembrane

Machupo virus, known to cause hemorrhagic fevers, enters human cells via binding with its envelope glycoprotein to transferrin receptor 1 (TfR). Similarly, the receptor interactions have been explored in biotechnological applications as a molecular system to ferry therapeutics across the cellular membranes and through the impenetrable blood–brain barrier that effectively blocks any such delivery into

Flexible regions in proteins, such as loops, cannot be represented by a single conformation. Instead, conformational ensembles are needed to provide a more global picture. In this context, identifying statistically meaningful conformations within an ensemble generated by loop sampling techniques remains an open problem. The difficulty is primarily related to the lack of structural data about these

RfaH is a compact two‐domain bacterial transcription factor that functions both as a regulator of transcription and an enhancer of translation. Underpinning the dual functional roles of RfaH is a partial but dramatic fold switch, which completely transforms the ~50‐amino acid C‐terminal domain (CTD) from an all‐α state to an all‐β state. The fold switch of the CTD occurs when RfaH binds to RNA polymerase

Resistance‐nodulation‐cell division family proteins are transmembrane proteins identified as large spectrum drug transporters involved in multidrug resistance. A prototypical case in this superfamily, responsible for antibiotic resistance in selected gram‐negative bacteria, is AcrB. AcrB forms a trimer using the proton motive force to efflux drugs, implementing a functional rotation mechanism. Unfortunately

Signal peptides help newly synthesized proteins reach the cell membrane or be secreted. As part of a biological process key to immune response and surveillance in humans, and associated with diseases, for example, Alzheimer, remnant signal peptides and other transmembrane segments are proteolyzed by the intramembrane aspartyl protease (IAP) enzyme family. Here, we identified IAP orthologs throughout

Lyme disease is the most widespread vector‐transmitted disease in North America and Europe, caused by infection with Borrelia burgdorferi sensu lato complex spirochetes. We report the solution NMR structure of the B. burgdorferi outer surface lipoprotein BBP28, a member of the multicopy lipoprotein (mlp) family. The structure comprises a tether peptide, five α‐helices and an extended C‐terminal loop

A major challenge for protein databases is reconciling information from diverse sources. This is especially difficult when some information consists of secondary, human‐interpreted rather than primary data. For example, the Swiss‐Prot database contains curated annotations of subcellular location that are based on predictions from protein sequence, statements in scientific articles, and published experimental

S‐adenosyl‐L‐methionine (SAM)‐dependent methyltransferases (MTases) are widely distributed among almost all organisms and often characterized with conserved Rossmann fold, TIM barrel, and D×G×G×G motif. However, some MTases show no methyltransferase activity. In the present study, the crystal structure of LepI, one MTase‐like enzyme isolated from A. flavus that catalyzes pericyclic reactions, was investigated

The Rad50‐Mre11 nuclease complex plays a vital role in DNA repair in all domains of life. It recognizes and processes DNA double‐strand breaks. Rad50 proteins fold into an extended structure with a 20 to 60 nm long coiled coil connecting a globular ABC ATPase domain with a zinc hook dimerization domain. A published structure of an archaeal Rad50 zinc hook shows coiled coils pointing away from each

We present a novel Java‐based program denominated PeptiDesCalculator for computing peptide descriptors. These descriptors include: redefinitions of known protein parameters to suite the peptide domain, generalization schemes for the global descriptions of peptide characteristics, as well as empirical descriptors based on experimental evidence on peptide stability and interaction propensity. The PeptiDesCalculator

Accurate prediction of protein secondary structure (alpha‐helix, beta‐strand and coil) is a crucial step for protein inter‐residue contact prediction and ab initio tertiary structure prediction. In a previous study, we developed a deep belief network‐based protein secondary structure method (DNSS1) and successfully advanced the prediction accuracy beyond 80%. In this work, we developed multiple advanced

Human interleukin‐6 (hIL‐6) is a multifunctional cytokine that regulates immune and inflammatory responses in addition to metabolic and regenerative processes and cancer. hIL‐6 binding to the IL‐6 receptor (IL‐6Rα) induces homodimerization and recruitment of the glycoprotein (gp130) to form a hexameric signaling complex. Anti‐IL‐6 and IL‐6R antibodies are clinically approved inhibitors of IL‐6 signaling

Activation of T cells triggers the expression of regulatory molecules like the programmed cell death 1 (PD1) protein. The association of PD1 with the natural ligands PDL1 and PDL2 induces an inhibitory signal that prevents T cells from proliferating and exerting effector functions. However, little is known about how the binding of the ligands induce the PD1 inhibitory signal over T cells effector functions

Expansins have the remarkable ability to loosen plant cell walls and cellulose material without showing catalytic activity and therefore have potential applications in biomass degradation. To support the study of sequence‐structure‐function relationships and the search for novel expansins, the Expansin Engineering Database (ExED, https://exed.biocatnet.de) collected sequence and structure data on expansins

N‐acetylglucosamine 6‐phosphate deacetylase (NagA) catalyzes the conversion of N‐acetylglucosamine‐6‐phosphate to glucosamine‐6‐phosphate in amino sugar catabolism. This conversion is an essential step in the catabolism of sialic acid in several pathogenic bacteria, including Pasteurella multocida, and thus NagA is identified as a potential drug target. Here, we report the unique structural features

Biosimilars offer an avenue for potential cost savings and enhanced patient access to various emerging therapies in a budget neutral way. Biosimilars of the granulocyte colony stimulating factor (GCSF) are an excellent example in this regard with as many as 18 versions of the drug being currently approved across globe for treatment of neutropenia. Here, we identified oxidation of the various methionine

Enhanced intracellular survival (Eis) proteins belonging to the superfamily of the GCN5‐related N‐acetyltransferases play important functions in mycobacterial pathogenesis. In Mycobacterium tuberculosis, Eis enhances the intracellular survival of the bacilli in macrophages by modulating the host immune response and is capable to chemically modify and inactivate aminoglycosides. In nontuberculous mycobacteria

With the development of various nanomaterial expected to be used in biomedical fields, it is more important to evaluate and understand their potential effects on biological system. In this work, two proteins with different structure, Villin Headpiece (HP35) with α‐helix structure and protofibrils Aβ1‐42 with five β‐strand chains, were selected and their interactions with silicene were studied by means

Hydrophobic association is the key contributor behind the formation of well packed core of a protein which is often believed to be an important step for folding from an unfolded chain to its compact functional form. While most of the protein folding/unfolding studies have evaluated the changes in the hydrophobic interactions during chemical denaturation, the role of hydrophilic amino acids in such

Natural products and natural product‐derived compounds have been widely used for pharmaceuticals for many years, and the search for new natural products that may have interesting activity is ongoing. Abyssomicins are natural product molecules that have antibiotic activity via inhibition of the folate synthesis pathway in microbiota. These compounds also appear to undergo a required [4 + 2] cycloaddition

This article reports on the results of research aimed to translate biometric 3D face recognition concepts and algorithms into the field of protein biophysics in order to precisely and rapidly classify morphological features of protein surfaces. Both human faces and protein surfaces are free‐forms and some descriptors used in differential geometry can be used to describe them applying the principles

The focal adhesion kinase (FAK) and the proline‐rich tyrosine kinase 2‐beta (PYK2) are implicated in cancer progression and metastasis and represent promising biomarkers and targets for cancer therapy. FAK and PYK2 are recruited to focal adhesions (FAs) via interactions between their FA targeting (FAT) domains and conserved segments (LD motifs) on the proteins Paxillin, Leupaxin, and Hic‐5. A promising

Dihydrolipoamide dehydrogenase (DLDH) is a mitochondrial enzyme that comprises an essential component of the pyruvate dehydrogenase complex. Lines of evidence have shown that many dehydrogenases possess unrelated actions known as moonlightings in addition to their oxidoreductase activity. As part of these activities, we have demonstrated that DLDH binds TiO2 as well as produces reactive oxygen species

Only about 0.3% of the entries in UniProt database have manually curated annotation. Annotation at the molecular level often relies on low‐throughput one‐protein‐at‐a‐time approach. Computational methods bridge this gap by assigning function based on sequence and/or fold similarity. Left‐handed beta helix (LbH) consists of three repeating six‐stranded beta‐strands forming an 18‐mer turn of the helix

It has been shown recently by Porter & Looger that a significant number of proteins exist that can form more than one stable fold. This note examines the sequences of these fold‐switching proteins by (a) calculating their foldability scores recently introduced by the present author and (b) comparing the propensity of chameleon sequences in fold switchers and in non fold switchers. It has been found

Isoflavonoid is one of the groups of flavonoids that play pivotal roles in the survival of land plants. Chalcone synthase (CHS), the first enzyme of the isoflavonoid biosynthetic pathway, catalyzes the formation of a common isoflavonoid precursor. We have previously reported that an isozyme of soybean CHS (termed GmCHS1) is a key component of the isoflavonoid metabolon, a protein complex to enhance

Cytoplasmic activation/proliferation‐associated protein (Caprin) proteins assume diverse functions in many important biological processes, including synaptic plasticity, stress response, innate immune response, and cellular proliferation. The Caprin family members are characterized by the presence of a highly conserved homologous region (HR1) at the N‐terminus and arginine‐glycine‐rich (RGG) boxes

High divergence in protein sequences makes the detection of distant protein relationships through homology‐based approaches challenging. Grouping protein sequences into families, through similarities in either sequence or 3‐D structure, facilitates in the improved recognition of protein relationships. In addition, strategically designed protein‐like sequences have been shown to bridge distant structural

CAPRI challenges offer a variety of blind tests for protein‐protein interaction prediction. In CAPRI Rounds 38‐45, we generated a set of putative binding modes for each target with an FFT‐based docking algorithm, and then scored and ranked these binding modes with a proprietary scoring function, ITScorePP. We have also developed a novel web server, Rebipp. The algorithm utilizes information retrieval