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Repurposing of FDA-approved drugs as autophagy inhibitors in tumor cells J. Biomol. Struct. Dyn. Pub Date : 2021-01-20 Kumari Prerna; Vikash Kumar Dubey
Abstract Autophagy and apoptosis are the two crucial processes of programmed cell death found in all eukaryotic cells; however, the elevated physiological stress in the tumor microenvironment leads to uncontrolled up-regulation in the process of autophagy. Available literatures suggest that inhibiting up-regulated autophagy in the cancerous cells may lead to the apoptosis and thereby culminate to tumor
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Rational design of PIN1 inhibitors for cancer treatment based on conformational diversity analysis and docking based virtual screening J. Biomol. Struct. Dyn. Pub Date : 2021-01-19 Julián Maggio; Maia Cabrera; Romina Armando; Patricio Chinestrad; Marina Pifano; Pablo Lorenzano Menna; Daniel E. Gomez; Diego L. Mengual Gómez
Abstract The parvulin PIN1 (peptidyl-prolyl cis-trans isomerase NIMA-interacting 1), is the only enzyme capable of isomerizing prolines of phospho-Serine/Threonine-Proline motifs. PIN1 binds to a subset of proteins and plays an essential role in regulating protein function post-phosphorylation control. Furthermore, the activity of PIN1 regulates the outcome of the signalling of proline-directed kinases
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Mining of Ebola virus genome for the construction of multi-epitope vaccine to combat its infection J. Biomol. Struct. Dyn. Pub Date : 2021-01-19 Uma Shankar; Neha Jain; Subodh Kumar Mishra; Md Fulbabu Sk; Parimal Kar; Amit Kumar
Abstract Ebola virus is the primary causative agent of viral hemorrhagic fever that is an epidemic disease and responsible for the massive premature deaths in humans. Despite knowing the molecular mechanism of its pathogenesis, to date, no commercial or FDA approved multiepitope vaccine is available against Ebola infection. The current study focuses on designing a multi-epitope subunit vaccine for
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Molecular mechanism study of EGFR allosteric inhibitors using molecular dynamics simulations and free energy calculations J. Biomol. Struct. Dyn. Pub Date : 2021-01-18 Xiaoyun Wu; Qian Guo; Qinlan Li; Shanhe Wan; Zhonghuang Li; Jiajie Zhang
ABTRACT The epidermal growth factor receptor (EGFR) kinase inhibitors Gefitinib, Erlotinib, Afatinib and Osimertinib have been approved for the treatments of non-small cell lung cancer patients harboring sensitive EGFR mutations, but resistance arises rapidly. To date all approved EGFR inhibitors are ATP-competitive inhibitors, highlighting the need for therapeutic agents with alternative mechanisms
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Dimeric phosphorylation of glyoxalase I alters its symmetry and substrate binding mechanism: simulation studies J. Biomol. Struct. Dyn. Pub Date : 2021-01-18 Lisa Michelle Barber; Zakir Hussain; Merlin Thomas; Andrew Hung
Abstract Glyoxalase I (GLO1) is a dimeric esterase of the glyoxalase system. Phosphorylation of the residue T106 has been found to inhibit GLO1 activity, and contribute to the onset of oxidative stress and cellular damage. This research uses multiple molecular dynamics simulations and automated docking of both GLO1 and dimerically phosphorylated GLO1 (p2-GLO1) to predict the initial structural differences
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Molecular docking and simulation studies of natural compounds of Vitex negundo L. against papain-like protease (PLpro) of SARS CoV-2 (coronavirus) to conquer the pandemic situation in the world J. Biomol. Struct. Dyn. Pub Date : 2021-01-18 Debasis Mitra; Devvret Verma; Bhaswatimayee Mahakur; Anshul Kamboj; Rakesh Srivastava; Sugam Gupta; Ajita Pandey; Bhawna Arora; Kumud Pant; P. Panneerselvam; Arabinda Ghosh; Durga P. Barik; Pradeep K. Das Mohapatra
Abstract The severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) is β-coronavirus that is responsible for the pandemic coronavirus disease 2019 (COVID-19) all over the world. The rapid spread of the novel SARS CoV-2 worldwide is raising a significant global public health issue with nearly 61.86 million people infected and 1.4 million deaths. To date, no specific drugs are available for the
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An in silico analysis of Ibuprofen enantiomers in high concentrations of sodium chloride with SARS-CoV-2 main protease J. Biomol. Struct. Dyn. Pub Date : 2021-01-18 C. M. Clemente; M. I. Freiberger; S. Ravetti; D. M. Beltramo; A. G. Garro
Abstract 2020 will be remembered worldwide for the outbreak of Coronavirus disease (COVID-19), which quickly spread until it was declared as a global pandemic. The main protease (Mpro) of SARS-CoV-2, a key enzyme in coronavirus, represents an attractive pharmacological target for inhibition of SARS-CoV-2 replication. Here, we evaluated whether the anti-inflammatory drug Ibuprofen, may act as a potential
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Structure analysis of the proteins associated with polyA repeat expansion disorders J. Biomol. Struct. Dyn. Pub Date : 2021-01-18 Rolando Hernandez; Julio C. Facelli
Abstract Repeat regions are low-complexity regions in the human genome that largely code for intrinsic disorder in proteins. Expansions outside the normal thresholds in repeat regions are likely to be pathogenic, leading to the so-called repeat expansion diseases. There have been numerous studies on the most common group of repeat expansion diseases, which are the polyglutamine (polyQ) repeat expansion
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Exploration of structural requirements for the inhibition of VEGFR-2 tyrosine kinase: Binding site analysis of type II, ‘DFG-out’ inhibitors J. Biomol. Struct. Dyn. Pub Date : 2021-01-18 Siddharth J. Modi; Vithal M. Kulkarni
Abstract The conserved three-dimensional structure of receptor tyrosine kinases (RTKs) has been varyingly observed in prokaryotes to humans that actively participate in the phosphorylation process of tyrosine residues in the protein, which results in the alteration of protein’s function. Mutation and transcriptional or post-translational modifications lead to a deregulation of kinases, which ultimately
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Identification of 1,2,3-triazole-phthalimide derivatives as potential drugs against COVID-19: a virtual screening, docking and molecular dynamic study J. Biomol. Struct. Dyn. Pub Date : 2021-01-18 Vanderlan Nogueira Holanda; Elton Marlon de Araújo Lima; Welson Vicente da Silva; Rafael Trindade Maia; Rafael de Lima Medeiros; Arabinda Ghosh; Vera Lúcia de Menezes Lima; Regina Celia Bressan Queiroz de Figueiredo
Abstract In this work we aimed to perform an in silico predictive screening, docking and molecular dynamic study to identify 1,2,3-triazole-phthalimide derivatives as drug candidates against SARS-CoV-2. The in silico prediction of pharmacokinetic and toxicological properties of hundred one 1,2,3-triazole-phtalimide derivatives, obtained from SciFinder® library, were investigated. Compounds that did
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Enhancing bactericidal strategy with selected aromatic compounds: in vitro and in silico study J. Biomol. Struct. Dyn. Pub Date : 2021-01-18 Aykut Oztekin; Kenan Karagoz; Sevki Adem; Veysel Comakli
Abstract β-Lactamases are enzymes that catalyze the hydrolysis of the β-lactam ring, resulting in loss of function in β-lactam antibiotics. In this report, the inhibition of β-lactamase enzyme by group-based selected aromatic compounds, especially containing flavone ring, was investigated in vitro and in silico. For this purpose, the inhibitory effects of 7-hydroxy-4'-nitroisoflavone, myricetin, formononetin
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Withanolides from Withania somnifera as an immunity booster and their therapeutic options against COVID-19 J. Biomol. Struct. Dyn. Pub Date : 2021-01-18 Pukar Khanal; Rupesh Chikhale; Yadu Nandan Dey; Ismail Pasha; Sharad Chand; Nilambari Gurav; Muniappan Ayyanar; B. M. Patil; Shailendra Gurav
Abstract Traditionally, Withania somnifera is widely used as an immune booster, anti-viral, and for multiple medicinal purposes. The present study investigated the withanolides as an immune booster and anti-viral agents against the coronavirus-19. Withanolides from Withania somnifera were retrieved from the open-source database, their targets were predicted using DIGEP-Pred, and the protein-protein
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In vivo/in silico insight into the effect of titanium dioxide nanoparticle on serum paraoxonase 1 activity in rat J. Biomol. Struct. Dyn. Pub Date : 2021-01-18 Hessameddin Mortazavi; Hossein Omidi-Ardali; Seyed Asadollah Amini; Javad Saffari-Chaleshtori; Keihan Ghatreh Samani
Abstract Serum paraoxonase1 (PON1) has special function in human body organism including the antioxidant and anti-atherogenic properties. In the present study, the effect of TiO2 nanoparticles on the activity and structure of the PON1 has been evaluated through in vivo and in silico methods. After treatments of the rats with different doses of TiO2 NPs, blood samples were collected and serum PON1 activity
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Molecular elucidation of pancreatic elastase inhibition by baicalein J. Biomol. Struct. Dyn. Pub Date : 2021-01-15 Debajeet Ghosh; Sneha Bansode; Rakesh Joshi; Baban Kolte; Rajesh Gacche
Abstract The serine protease, elastase exists in various forms and plays diverse roles in the human body. Pharmacological inhibition of elastase has been investigated for its therapeutic role in managing conditions such as diabetes, pneumonia and arthritis. Sivelestat, a synthetic molecule, is the only elastase inhibitor to have been approved by any major drug regulatory authority (PMDA, in this case)
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Bacillus species; a potential source of anti-SARS-CoV-2 main protease inhibitors J. Biomol. Struct. Dyn. Pub Date : 2021-01-15 Sadia Alam; Shahida Sadiqi; Maimoona Sabir; Sobia Nisa; Sajjad Ahmad; Sumra Wajid Abbasi
Abstract The COVID-19 being a preconized global pandemic by the World Health Organization needs persuasive immediate research for possible medications. The present study was carried out with a specific aim to computationally evaluate and identify compounds derived from Bacillus species as the plausible inhibitors against 3-chymotrypsin-like main protease (3CLpro) or main protease (MPro), which is a
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Prospecting for Cressa cretica to treat COVID-19 via in silico molecular docking models of the SARS-CoV-2 J. Biomol. Struct. Dyn. Pub Date : 2021-01-15 Sapan Shah; Dinesh Chaple; Sumit Arora; Subhash Yende; Chetan Mehta; Usha Nayak
Abstract The severe acute respiratory syndrome COVID-19 declared as a global pandemic by the World Health Organization has become the present wellbeing worry to the whole world. There is an emergent need to search for possible medications. Cressa cretica is reported to show antitubercular, antibacterial and expectorant property. In this research, we aim to prospect the COVID-19 main protease crystal
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Oncogenic potential of ATAD2 in stomach cancer and insights into the protein-protein interactions at its AAA + ATPase domain and bromodomain J. Biomol. Struct. Dyn. Pub Date : 2021-01-13 Aditi Nayak; Sugandh Kumar; Shivaram Prasad Singh; Asima Bhattacharyya; Anshuman Dixit; Anasuya Roychowdhury
Abstract ATAD2 has recently been shown to promote stomach cancer. However, nothing is known about the functional network of ATAD2 in stomach carcinogenesis. This study illustrates the oncogenic potential of ATAD2 and the participation of its ATPase and bromodomain in stomach malignancy. Expression of ATAD2 in stomach cancer is analyzed by in silico and in vitro techniques including western blot and
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Enfuvirtide, an HIV-1 fusion inhibitor peptide, can act as a potent SARS-CoV-2 fusion inhibitor: an in silico drug repurposing study J. Biomol. Struct. Dyn. Pub Date : 2021-01-13 Khadijeh Ahmadi; Alireza Farasat; Mosayeb Rostamian; Behrooz Johari; Hamid Madanchi
Abstract Regarding the urgency of therapeutic measures for coronavirus disease 2019 (COVID-19) pandemic, the use of available drugs with FDA approval is preferred because of the less time and cost required for their development. In silico drug repurposing is an accurate way to speed up the screening of the existing FDA-approved drugs to find a therapeutic option for COVID-19. The similarity in SARS-CoV-2
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Insights in the structural understanding of amyloidogenicity and mutation-led conformational dynamics of amyloid beta (Aβ) through molecular dynamics simulations and principal component analysis J. Biomol. Struct. Dyn. Pub Date : 2021-01-13 Sriram Srinivasa Raghavan; Saleem Iqbal; Ayyadurai Niraikulam; Krishnasamy Gunasekaran
Abstract Abnormal protein aggregation in the nervous tissue leads to several neurodegenerative disorders like Alzheimer’s disease (AD). In AD, accumulation of the amyloid beta (Aβ) peptide is proposed to be an early important event in pathogenesis. Significant research efforts are devoted so as to understand the Aβ misfolding and aggregation. Molecular dynamics (MD) simulations complement experiments
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In silico analysis of antiviral phytochemicals efficacy against Epstein–Barr virus glycoprotein H J. Biomol. Struct. Dyn. Pub Date : 2021-01-13 Shweta Jakhmola; Zaved Hazarika; Anupam Nath Jha; Hem Chandra Jha
Abstract Epstein–Barr virus is a tumor-associated, enveloped virus with glycoprotein receptor gHgL on its surface. gH attaches to epithelial or B cells and mediates internalization. Till date, no specific anti-EBV FDA approved drug is available. Targeting gH may aid in designing virus-specific therapeutics and reducing the drug induced complications in host. We investigated the influence of antiviral
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Exploring of paritaprevir and glecaprevir resistance due to A156T mutation of HCV NS3/4A protease: molecular dynamics simulation study J. Biomol. Struct. Dyn. Pub Date : 2021-01-11 Thitiya Boonma; Bodee Nutho; Nitchakan Darai; Thanyada Rungrotmongkol; Nadtanet Nunthaboot
Abstract Hepatitis C virus (HCV) NS3/4A serine protease is a promising drug target for the discovery of anti-HCV drugs. However, its amino acid mutations, particularly A156T, commonly lead to rapid emergence of drug resistance. Paritaprevir and glecaprevir, the newly FDA-approved HCV drugs, exhibit distinct resistance profiles against the A156T mutation of HCV NS3/4A serine protease. To illustrate
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Novel copper complexes of metronidazole and metronidazole benzoate: synthesis, characterization, biological and computational studies J. Biomol. Struct. Dyn. Pub Date : 2021-01-11 Bushra Rafique; Kainat Shafique; Sabahat Hamid; Saima Kalsoom; Muhammad Hashim; Bushra Mirza; Laila Jafri; Mudassir Iqbal
Abstract Synthesis and characterization of novel copper complexes of metronidazole benzoate (MTZ Benz), metronidazole (MTZ) in the presence of another ligand; dichloroacetic acid (DCA) were compared and reported in the present work. Different bacterial and fungus strains were ascertained to evaluate the biological potency of the synthesized complexes, that is, Escherichia coli, Bordetella bronceptica
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Predictive medicinal metabolites from Momordica dioica against comorbidity related proteins of SARS-CoV-2 infections J. Biomol. Struct. Dyn. Pub Date : 2021-01-11 Chavan Sakshi; A. Harikrishnan; Selvakumar Jayaraman; Ahana Roy Choudhury; V. Veena
Abstract Momordica dioica have proven medicinal potential of antidiabetic, antiviral and immune stimulating properties. Flavonoids and triterpenoids from M. dioica were more extensively investigated for antiviral, antidiabetic and immunomodulatory activities. In this present study, we have predicted the reported bioactive flavonoids and triterpenoids of the plant against the SARS-CoV-2 main protease
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Identification of novel potential cyclooxygenase-2 inhibitors using ligand- and structure-based virtual screening approaches J. Biomol. Struct. Dyn. Pub Date : 2021-01-10 Josiane V. Cruz; Silvana Giuliatti; Levy B. Alves; Raí C. Silva; Elenilze F. B. Ferreira; Njogu M. Kimani; Carlos H. T. P. Silva; João S. N. de Souza; José M. Espejo-Román; Cleydson B. R. Santos
Abstract Cyclooxygenase 2 (COX-2) is a well-established target for the design of anti-inflammatory intermediates. Celecoxib was selected as a template molecule to perform ligand-based virtual screening, i.e. to search for structures with similarity in shape and electrostatic potential, with a gradual increase in accuracy through the combined fitting of several steps using eight commercial databases
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ACE2-derived peptides interact with the RBD domain of SARS-CoV-2 spike glycoprotein, disrupting the interaction with the human ACE2 receptor J. Biomol. Struct. Dyn. Pub Date : 2021-01-10 Pedro F. N. Souza; Jackson L. Amaral; Leandro P. Bezerra; Francisco E. S. Lopes; Valder N. Freire; Jose T. A. Oliveira; Cleverson D. T. Freitas
Abstract Vaccines could be the solution to the current SARS-CoV-2 outbreak. However, some studies have shown that the immunological memory only lasts three months. Thus, it is imperative to develop pharmacological treatments to cope with COVID-19. Here, the in silico approach by molecular docking, dynamic simulations and quantum biochemistry revealed that ACE2-derived peptides strongly interact with
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Searching for potential drugs against SARS-CoV-2 through virtual screening on several molecular targets J. Biomol. Struct. Dyn. Pub Date : 2021-01-08 Joyce S. F. D. Almeida; Fernanda D. Botelho; Felipe R. de Souza; Marcelo C. dos Santos; Arlan da Silva Goncalves; Rodrigo L. B. Rodrigues; Monique Cardozo; Daniel A. S. Kitagawa; Leandro A. Vieira; Raphael S. F. Silva; Samir F. A. Cavalcante; Leonardo da C. Bastos; Mariana de O. T. Nogueira; Priscila I. R. de Santana; Juliana de O. C. Brum; Eugenie Nepovimova; Kamil Kuca; Steven R. LaPlante; Erick
Abstract The acute respiratory syndrome caused by the SARS-CoV-2, known as COVID-19, has been ruthlessly tormenting the world population for more than six months. However, so far no effective drug or vaccine against this plague have emerged yet, despite the huge effort in course by researchers and pharmaceutical companies worldwide. Willing to contribute with this fight to defeat COVID-19, we performed
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Influence of the dimensionality of the periodic boundary conditions on the transport of a drug–peptide complex across model cell membranes J. Biomol. Struct. Dyn. Pub Date : 2021-01-08 Nikoleta Ivanova; Anela Ivanova
Abstract Many research efforts are devoted to improving the efficiency of chemotherapy. One of the aspects is to facilitate the transport of drugs across the cell membranes by attaching the therapeutics to a carrier molecule. The current study focuses on computational investigation of such a system with doxorubicin as the model drug, which is covalently bound to a cell-penetrating peptide. The correct
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Highly potent anti-malarial activity of benzopyrano(4,3-b)benzopyran derivatives and in silico interaction analysis with putative target Plasmodium falciparum lactate dehydrogenase J. Biomol. Struct. Dyn. Pub Date : 2021-01-08 Nishant Joshi; Rahul Hada; Sonal Gupta; Juveria Khan; Jeremy Dobrowolski; Pawan K. Dhar; Naresh Kumar; Shailja Singh
Abstract Malaria infection caused by Plasmodium falciparum is majorly responsible for millions of deaths in humans every year. Moreover, a rapid increase in resistance to existing drugs has posed an urgent need for new anti-malarials. Herein, we report the highly potent anti-malarial activity of benzopyrano(4,3-b)benzopyran derivatives, inspired from naturally occurring dependensin against chloroquine
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Interactions of large T-Antigen (LT) protein of polyomaviruses with p53 unfold their cancerogenic potential J. Biomol. Struct. Dyn. Pub Date : 2021-01-08 Caroline Kellogg; Valentina L. Kouznetsova; Igor F. Tsigelny
Abstract Polyomaviruses such as Simian Virus 40 (SV40) and John Cunningham Virus (JCV) have been extensively studied for their potential role in aiding oncogenic transformation. One of the mechanisms through which they do this is by inactivating p53, a known tumor suppressor, through one of their viral proteins, large T-antigen (LT). However, these two viruses represent only a fraction of existing
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Identification of potential SARS-CoV-2 Mpro inhibitors integrating molecular docking and water thermodynamics J. Biomol. Struct. Dyn. Pub Date : 2021-01-08 M. Elizabeth Sobhia; Ketan Ghosh; Srikanth Sivangula; Siva Kumar; Harmanpreet Singh
Abstract The COVID-19 pandemic is an ongoing global health emergency caused by a newly discovered coronavirus SARS-CoV-2. The entire scientific community across the globe is working diligently to tackle this unprecedented challenge. In silico studies have played a crucial role in the current situation by expediting the process of identification of novel potential chemotypes targeting the viral receptors
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Structural aspects of β-glucosidase of Myceliophthora thermophila (MtBgl3c) by homology modelling and molecular docking J. Biomol. Struct. Dyn. Pub Date : 2021-01-08 Anica Dadwal; Vishal Singh; Shilpa Sharma; Tulasi Satyanarayana
Abstract Cellulases are the enzymes with diverse range of industrial applications. Cellulases degrade cellulose into monomeric glucose units by hydrolysing β-1,4-glycosidic bonds. There are three components of cellulases: a) endoglucanase, b) exoglucanase and c) β-glucosidase which act synergistically in cellulose bioconversion. The cellulases are the third largest industrial enzymes with a great potential
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Unravelling the molecular basis of AM-6494 high potency at BACE1 in Alzheimer’s disease: an integrated dynamic interaction investigation J. Biomol. Struct. Dyn. Pub Date : 2021-01-07 Samuel C. Ugbaja; Patrick Appiah-Kubi; Monsurat M. Lawal; Nelisiwe S. Gumede; Hezekiel M. Kumalo
Abstract β-amyloid precursor protein cleaving enzyme1 (BACE1) has prominently been an important drug design target implicated in Alzheimer’s disease pathway. The failure rate of most of the already tested drugs at different clinical phases remains a major concern. Recently, AM-6494 was reported as a novel potent, highly selective, and orally effective inhibitor against BACE1. AM-6494 displayed no alteration
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Shell disorder and the HIV vaccine mystery: lessons from the legendary Oswald Avery J. Biomol. Struct. Dyn. Pub Date : 2021-01-07 Gerard Kian-Meng Goh; Vladimir N. Uversky
Abstract The search for a human immunodeficiency virus (HIV) vaccine has spanned nearly four decades without much success. A much needed paradigm shift can be found in the abnormally high levels of intrinsic disorder in the outer shells of HIVs, the hepatitis C virus (HCV), and herpes simplex viruses (HSVs), for which successful vaccines have not been established. On the other hand, this feature (high
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Exploring the binding interactions of janus green blue with serum albumins from spectroscopic and calorimetric studies aided by in silico calculations J. Biomol. Struct. Dyn. Pub Date : 2021-01-07 Saumen Saha; Snehasish Bhattacharjee; Joydeep Chowdhury
Abstract Binding interactions of the phenazinium dye Janus green blue (JGB) with human and bovine serum albumins (HSA and BSA) have been explored for the first time from multi-spectroscopic and calorimetric measurements aided by in silico calculations. The formation of ground state complexes between JGB and the respective serum albumins have been suggested from the UV–Vis and steady-state fluorescence
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Utilization of O/S-doped graphene nanoclusters for ultrasensitive detection of flurane derivatives-DFT investigations J. Biomol. Struct. Dyn. Pub Date : 2021-01-07 Jamelah S. Al-Otaibi; Aljawhara H. Almuqrin; Y. Sheena Mary; Y. Shyma Mary
Abstract Nanocluster based drug delivery systems are very useful in modern medical treatment and interaction mechanism of desflurane (DES), isoflurane ISO), sevoflurane (SEV) over carboxyl substituted graphene-doped with O and S atoms were investigated in the present study. Different electronic and chemical properties of adsorbed desflurane, isoflurane and sevoflurane with nanoclusters are analyzed
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Identification of novel potential ricin inhibitors by virtual screening, molecular docking, molecular dynamics and MM-PBSA calculations: a drug repurposing approach J. Biomol. Struct. Dyn. Pub Date : 2021-01-07 Fernanda D. Botelho; Marcelo C. Santos; Arlan S. Gonçalves; Tanos C. C. França; Steven R. LaPlante; Joyce S. F. D. de Almeida
Abstract Ricin is a potent cytotoxin with no available antidote. Its catalytic subunit, RTA, damages the ribosomal RNA (rRNA) of eukaryotic cells, preventing protein synthesis and eventually leading to cell death. The combination between easiness of obtention and high toxicity turns ricin into a potential weapon for terrorist attacks, urging the need of discovering effective antidotes. On this context
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Virtual screening and repurposing of FDA-approved drugs from ZINC database to identify potential autophagy inhibitors exploiting autophagy related 4A cysteine peptidase as a target: potential as novel anti-cancer molecule. J. Biomol. Struct. Dyn. Pub Date : 2021-01-07 Umesh; Kumari Prerna; Vikash Kumar Dubey
Abstract Cancer cells utilize extensive autophagy in effort to adapt to high metabolic stress. This indicates that impairing the high autophagic flux might be an attractive target for cancer therapy. Autophagy related gene 4A (ATG4A) is a key player for autophagy and its inhibition may help in tumor clearance. The present study aims to screen candidate drugs from FDA-approved drugs, a subset of Zinc
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Inhibition of biofilm formation, quorum sensing and other virulence factors in Pseudomonas aeruginosa by polyphenols of Gynura procumbens leaves J. Biomol. Struct. Dyn. Pub Date : 2021-01-06 Zulkar Nain; Fariha Jasin Mansur; Shifath Bin Syed; Md Ariful Islam; Hiroyuki Azakami; Md Rezuanul Islam; Mohammad Minnatul Karim
Abstract Quorum sensing (QS) enables virulence factors in bacteria for biofilm formation and pathogenic invasion. Therefore, quorum quenching (QQ), disruption of QS circuit, becomes an alternative antimicrobial therapy. In this study, leaf extract of Gynura procumbens (GP) was used to inhibit biofilm and virulent factors in Pseudomonas aeruginosa. The extract inhibited the biofilm production (p ≤ 0
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In silico design of multi-epitope-based peptide vaccine against SARS-CoV-2 using its spike protein J. Biomol. Struct. Dyn. Pub Date : 2021-01-06 Debarghya Mitra; Janmejay Pandey; Alok Jain; Shiv Swaroop
Abstract SARS-CoV-2 has been efficient in ensuring that many countries are brought to a standstill. With repercussions ranging from rampant mortality, fear, paranoia, and economic recession, the virus has brought together countries to look at possible therapeutic countermeasures. With prophylactic interventions possibly months away from being particularly effective, a slew of measures and possibilities
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Monte-Carlo method-based QSAR model to discover phytochemical urease inhibitors using SMILES and GRAPH descriptors J. Biomol. Struct. Dyn. Pub Date : 2021-01-06 Kumar Sambhav Chopdar; Ganesh Chandra Dash; Pranab Kishor Mohapatra; Binata Nayak; Mukesh Kumar Raval
Abstract Urease inhibitors are known to play a vital role in the field of medicine as well as agriculture. Special attention is attributed to the development of novel urease inhibitors with a view to treat the Helicobacter pylori infection. Amongst a number of urease inhibitors, a large number of molecules fail in vivo and in clinical trials due to their hydrolytic instability and toxicity profile
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In-silico identification of potential inhibitors targeting the DNA binding domain of estrogen receptor α for the treatment of hormone therapy-resistant breast cancer J. Biomol. Struct. Dyn. Pub Date : 2021-01-06 El Mehdi Bouricha; Mohammed Hakmi; Jihane Akachar; Fouad Zouaidia; Azeddine Ibrahimi
Abstract Estrogen receptor α (ERα) plays a critical role in breast cancer (BC) development. The standard therapeutic strategies for ERα- positive (ERα+) BC consist of impairing ERα signalling pathway by either estrogen competitors blocking its interaction with the ligand binding domain (LBD) or agents inhibiting the production of estrogen. These strategies are limited by many factors that lead to constitutive
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Virtual screening of curcumin and its analogs against the spike surface glycoprotein of SARS-CoV-2 and SARS-CoV J. Biomol. Struct. Dyn. Pub Date : 2021-01-05 Ashish Patel; Malathi Rajendran; Ashish Shah; Harnisha Patel; Suresh B. Pakala; Prashanthi Karyala
Abstract COVID-19, a new pandemic caused by SARS-CoV-2, was first identified in 2019 in Wuhan, China. The novel corona virus SARS-CoV-2 and the 2002 SARS-CoV have 74% identity and use similar mechanisms to gain entry into the cell. Both the viruses enter the host cell by binding of the viral spike glycoprotein to the host receptor, angiotensin converting enzyme 2 (ACE2). Targeting entry of the virus
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Molecular mechanism of inhibition of COVID-19 main protease by β-adrenoceptor agonists and adenosine deaminase inhibitors using in silico methods J. Biomol. Struct. Dyn. Pub Date : 2021-01-05 Pushyaraga P. Venugopal; Debashree Chakraborty
Abstract Novel coronavirus (COVID-19) responsible for viral pneumonia which emerged in late 2019 has badly affected the world. No clinically proven drugs are available yet as the targeted therapeutic agents for the treatment of this disease. The viral main protease which helps in replication and transcription inside the host can be an effective drug target. In the present study, we aimed to discover
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Computational studies of membrane pore formation induced by Pin2 J. Biomol. Struct. Dyn. Pub Date : 2021-01-05 José-Luis Velasco-Bolom; Ramón Garduño-Juárez
Abstract Understanding, at the molecular level, the effect of AMPs on biological membranes is of crucial importance given the increasing number of multidrug-resistant bacteria. Being part of an ancient type of innate immunity system, AMPs have emerged as a potential solution for which bacteria have not developed resistance. Traditional antibiotics specifically act on biosynthetic pathways, while AMPs
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Shedding light on the bimolecular interactions of Cafaminol and human serum albumin: spectroscopic characterization and in-silico investigation J. Biomol. Struct. Dyn. Pub Date : 2021-01-04 Negar Parvizi; Delara Mohammad-Aghaie; Mohammad Navid Soltani Rad; Somayeh Behrouz; Mohamad Mehdi Alavianmehr
Abstract Cafaminol, also known as methylcoffanolamine, is a vasoconstrictor and anticatarrhal of the methylxanthine family, which is used as a nasal decongestant. This study aimed to investigate the interaction mechanisms of human serum albumin (HSA) with Cafaminol, through several spectroscopic (fluorescence quenching, UV-visible absorption, and circular dichroism (CD) spectroscopies) and molecular
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Virtual repurposing of ursodeoxycholate and chenodeoxycholate as lead candidates against SARS-Cov2-Envelope protein: A molecular dynamics investigation J. Biomol. Struct. Dyn. Pub Date : 2020-12-31 Reena Yadav; Chinmayee Choudhury; Yashwant Kumar; Alka Bhatia
Abstract Drug repurposing is an apt choice to combat the currently prevailing global threat of COVID-19, caused by SARS-Cov2in absence of any specific medication/vaccine. The present work employs state of art computational methods like homology modelling, molecular docking and molecular dynamics simulations to evaluate the potential of two widely used surfactant drugs namely chenodeoxycholate(CDC)
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Fisetin 8-C-glucoside as entry inhibitor in SARS CoV-2 infection: molecular modelling study J. Biomol. Struct. Dyn. Pub Date : 2020-12-31 Abha Mishra; Upinder Kaur; Amit Singh
Abstract Coronaviruses are RNA viruses that infect varied species including humans. TMPRSS2 is gateway for SARS CoV-2 entry into the host cell. It causes proteolytic activation of spike protein and discharge of the peptide into host cell. The TMPRSS2 inhibition could be one of the approaches to stop the viral entry, therefore, interaction pattern and binding energies for Fisetin and TMPRSS2 have been
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Revealing the cholinergic inhibition mechanism of Alzheimer’s by galantamine: a metadynamics simulation study J. Biomol. Struct. Dyn. Pub Date : 2020-12-31 Shibaji Ghosh; Kalyanashis Jana; Padmaja D. Wakchaure; Bishwajit Ganguly
Abstract Galantamine is one of the approved drugs based on the cholinergic hypothesis for the symptomatic treatment of mild to moderate Alzheimer’s disease (AD). The etiology of AD is not fully known; however, the reported cholinergic hypothesis suggests the inadequate synthesis of the neurotransmitter acetylcholine (ACh) is responsible for this disease. The crystal structure of galantamine bound human
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Ensemble-based high-throughput virtual screening of natural ligands using the Super Natural-II database against cell-wall protein dTDP-4-dehydrorhamnose reductase (RmlD) in Mycobacterium tuberculosis J. Biomol. Struct. Dyn. Pub Date : 2020-12-31 Rahul Ravichandran; Nor Farrah Wahidah Ridzwan; Saharuddin Bin Mohamad
Abstract The disease Tuberculosis (TB) is caused by a bacterium called Mycobacterium tuberculosis (Mtb). The bacterial cell-wall consists of peptidoglycan layer maintains the cellular integrity and cell viability. The main problem resides in the cell cycle of Mycobacterium tuberculosis in its quiescent form which is not targeted by any drugs hence there is an immediate need for new antibiotics to target
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Computational-aided design: minimal peptide sequence to block dengue virus transmission into cells J. Biomol. Struct. Dyn. Pub Date : 2020-12-31 Aathe Cangaree Arumugam; Fatima Ezzahra Agharbaoui; Ahmad Suhail Khazali; Rohana Yusof; Noorsaadah Abd Rahman; Abdullah Al Hadi Ahmad Fuaad
Abstract Dengue virus (DV) infection is one of the main public health concerns, affecting approximately 390 million people worldwide, as reported by the World Health Organization. Yet, there is no antiviral treatment for DV infection. Therefore, the development of potent and nontoxic anti-DV, as a complement for the existing treatment strategies, is urgently needed. Herein, we investigate a series
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Understanding the impact of anticancer halogenated inhibitors and various functional groups (X = Cl, F, CF3, CH3, NH2, OH, H) of casein kinase 2 (CK2) J. Biomol. Struct. Dyn. Pub Date : 2020-12-29 Palanisamy; Duraisamy Thirumeignanam
Abstract Main focus of study is to understand potency of halogen (X = Br) atom that exists in tetrabromobenzotriazole (TBB) derivatives of crystal CK2 ligand along with hinge region amino acids (VAL45, PHE113, GLU114, VAL116, ASN118) through interaction energy analysis. In turn to attain profound insight on nature of stabilization of core CK2 ligands: 1ZOE-L1, 1ZOG-L2, 1ZOH-L3, 2OXX-L4, 2OXY-L5, 3KXG-L6
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In silico analysis of phytochemicals as potential inhibitors of proteases involved in SARS-CoV-2 infection J. Biomol. Struct. Dyn. Pub Date : 2020-12-29 Palaniyandi Umadevi; Subramanian Manivannan; Abdulkabeer Muhammed Fayad; Sreekumar Shelvy
Abstract In silico analysis of six phytochemicals, flabelliferin, marmelosin, piperine, ocimin, curcumin and leucoanthocyanin, along with three drug compounds, nelfinavir, remdesivir and hydroxychloroquine, as positive control against drug targets of one SARS-CoV-2 viral protease, COVID-19 main protease (SARS CoV-2 3CLpro/Mpro), two coronavirus proteases, SARS-CoV main peptidase (SARS CoV Mpro), SARS-CoV
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Small molecule stabilization of non-native protein-protein interactions of SARS-CoV-2 N protein as a mechanism of action against COVID-19 J. Biomol. Struct. Dyn. Pub Date : 2020-12-28 Julián F. Fernández; Martín J. Lavecchia
Abstract The outbreak of COVID-19, the disease caused by SARS-CoV-2, continues to affect millions of people around the world. The absence of a globally distributed effective treatment makes the exploration of new mechanisms of action a key step to address this situation. Stabilization of non-native Protein-Protein Interactions (PPIs) of the nucleocapsid protein of MERS-CoV has been reported as a valid
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Dual inhibition of SARS-CoV-2 spike and main protease through a repurposed drug, rutin J. Biomol. Struct. Dyn. Pub Date : 2020-12-27 Anchala Kumari; Vikrant Singh Rajput; Priya Nagpal; Himanshi Kukrety; Sonam Grover; Abhinav Grover
Abstract The global health emergency caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to alarming numbers of fatalities across the world. So far the researchers worldwide have not been able to discover a breakthrough in the form of a potent drug or an effective vaccine. Therefore, it is imperative to discover drugs to curb the ongoing menace. In silico approaches using
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Prediction of potential inhibitors against SARS-CoV-2 endoribonuclease: RNA immunity sensing J. Biomol. Struct. Dyn. Pub Date : 2020-12-27 Nihad A. M. Al-Rashedi; Murad G. Munahi; Laith AH ALObaidi
Abstract The World Health Organization has classified the COVID-19 outbreak a pandemic which is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and declared it a global health emergency. Repurposing drugs with minimum side effects are one approach to quickly respond in attempt to prevent the spread of COVID-19. SARS-CoV-2 encodes several RNA processing enzymes that are unusual
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Design and in silico study of the novel coumarin derivatives against SARS-CoV-2 main enzymes J. Biomol. Struct. Dyn. Pub Date : 2020-12-27 Mücahit Özdemir; Baybars Köksoy; Deniz Ceyhan; Koray Sayın; Erol Erçağ; Mustafa Bulut; Bahattin Yalçın
Abstract The novel coronavirus (SARS-CoV-2) causes severe acute respiratory syndrome and can be fatal. In particular, antiviral drugs that are currently available to treat infection in the respiratory tract have been experienced, but there is a need for new antiviral drugs that are targeted and inhibit coronavirus. The antiviral properties of organic compounds found in nature, especially coumarins
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Computational approach to explore the inhibitory potential of biologically derived compounds against Spodoptera litura vitellogenin receptor (VgR) using structure based virtual screening and molecular dynamics J. Biomol. Struct. Dyn. Pub Date : 2020-12-24 Veeranarayanan Surya Aathmanathan; Velusamy Arumugam; Muthukalingan Krishnan
Abstract In the everlasting combat against the pests of agricultural importance, it is essential to come up with a novel strategy for pest control. This can be achieved through understanding the insect pest at cellular and molecular levels. Vitellogenin (Vg) and vitellogenin receptor (VgR) are essential for successful reproduction in insect. The N-terminal Ligand Binding Domain (LBD) of VgR is responsible
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Quantitative structure activity relationship studies of novel hydrazone derivatives as α-amylase inhibitors with index of ideality of correlation J. Biomol. Struct. Dyn. Pub Date : 2020-12-24 Meenakshi Duhan; Jayant Sindhu; Parvin Kumar; Meena Devi; Rahul Singh; Ramesh Kumar; Sohan Lal; Ashwani Kumar; Sudhir Kumar; Khalid Hussain
Abstract The present manuscript describes the synthesis, α-amylase inhibition, in silico studies and in-depth quantitative structure–activity relationship (QSAR) of a library of aroyl hydrazones based on benzothiazole skeleton. All the compounds of the developed library are characterized by various spectral techniques. α‐Amylase inhibitory potential of all compounds has been explored, where compound
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Role of Thr199 residue in human β-carbonic anhydrase-II pH-dependent activity elucidated by microsecond simulation analysis J. Biomol. Struct. Dyn. Pub Date : 2020-12-24 Pulala Raghuveer Yadav; Syed Hussain Basha; Pavan Kumar Pindi
Abstract Carbonic anhydrases catalyze the reversible hydration of carbon dioxide to form bicarbonate, a reaction required for many functions such as carbon assimilation, pH acid–base homeostasis, respiration and photosynthesis via a zinc-hydroxide mechanism for carbon dioxide hydration. In earlier studies, it was revealed that Carbonic anhydrases are inactive at pH 7.5 and active at pH 8.4. This steep
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Novel P,C-orthopalladated complexes containing histidine and phenylalanine amino acids: synthesis, DNA and BSA interactions, in vitro antitumoral activity and molecular docking approach J. Biomol. Struct. Dyn. Pub Date : 2020-12-24 Sara Hashemi; Kazem Karami; Zeinab Saberi Dehkordi; Amir Abbas Momtazi-Borojeni; Seyed Alireza Esmaeili
Abstract Novel [Pd(o-CH2C6H4P(o-tolyl)2)(histidine)] (1) and [Pd(o-CH2C6H4P(o tolyl)2)(phenylalanine)] (2) P,C-orthopalladated complexes have been prepared and characterized by elemental analysis, IR and NMR spectroscopy. To study the stability of the compounds in biological media, the complexes were incubated in Tris buffer during 10 days. The absorbance of the compounds remained constant, which confirmed