scholarly journals Absolute Protein Binding Free Energy Simulations for Ligands with Multiple Poses, a Thermodynamic Path That Avoids Exhaustive Enumeration of the Poses

2019 ◽  
Vol 41 (1) ◽  
pp. 56-68 ◽  
Author(s):  
Yoshitake Sakae ◽  
Bin W. Zhang ◽  
Ronald M. Levy ◽  
Nanjie Deng
Keyword(s):  
Free Energy ◽  
Protein Binding ◽  
Binding Free Energy ◽  
Energy Simulations

scholarly journals New Tools for Conformational and Binding Free Energy Simulations

2019 ◽  
Vol 116 (3) ◽  
pp. 142a
Author(s):  
Giacomo Fiorin ◽  
Grace Brannigan ◽  
Jérôme Hénin
Keyword(s):  
Free Energy ◽  
Binding Free Energy ◽  
Energy Simulations

scholarly journals On the electrostatic component of protein-protein binding free energy

2008 ◽  
Vol 1 (1) ◽  
pp. 2 ◽  
Author(s):  
Kemper Talley ◽  
Carmen Ng ◽  
Michael Shoppell ◽  
Petras Kundrotas ◽  
Emil Alexov
Keyword(s):  
Free Energy ◽  
Protein Binding ◽  
Binding Free Energy ◽  
Electrostatic Component

scholarly journals Investigation of the anti-TB potential of selected alkaloid constituents using molecular docking approach

2020 ◽  
Author(s):  
Mohammad Kawsar Sharif Siam ◽  
Mohammad Umer Sharif Shohan ◽  
Zaira Zafroon
Keyword(s):  
Free Energy ◽  
Mycobacterium Tuberculosis ◽  
Molecular Docking ◽  
Protein Binding ◽  
Binding Free Energy ◽  
Chemical Constituents ◽  
Biological Evaluation ◽  
Natural Sources ◽  
Docking Score ◽  
Docking Approach

AbstractMycobacterium tuberculosis, the leading bacterial killer disease worldwide, causes Human tuberculosis (TB). Due to the growing problem of drug resistant Mycobacterium tuberculosis strains, new anti-TB drugs are urgently needed. Natural sources such as plant extracts have long played an important role in tuberculosis management and can be used as a template to design new drugs. A wide screening of natural sources is time consuming but the process can be significantly sped up using molecular docking. In this study, we used a molecular docking approach to investigate the interactions between selected natural constituents and three proteins MtPanK, MtDprE1 and MtKasA involved in the physiological functions of Mycobacterium tuberculosis which are necessary for the bacteria to survive and cause disease. The molecular docking score, a score that accounts for the binding affinity between a ligand and a target protein, for each protein was calculated against 150 chemical constituents of different classes to estimate the binding free energy. The docking scores represent the binding free energy. The best docking scores indicates the highest ligand protein binding which is indicated by the lowest energy value. Among the natural constituents, Shermilamine B showed a docking score of - 8.5kcal/mol, Brachystamide B showed a docking score of −8.6 kcal/mol with MtPanK, Monoamphilectine A showed a score of −9.8kcal/mol with MtDprE1.These three compounds showed docking scores which were superior to the control inhibitors and represent the opportunity of in vitro biological evaluation and anti-TB drug design. Consequently, all these compounds belonged to the alkaloid class. Specific interactions were studied to further understand the nature of intermolecular bonds between the most active ligands and the protein binding site residues which proved that among the constituents monoamphilectine A and Shermilamine B show more promise as Anti-TB drugs. Furthermore, the ADMET properties of these compounds or ligands showed that they have no corrosive or carcinogenic parameters.Graphical Abstract

scholarly journals Molecular simulation of SARS-CoV-2 spike protein binding to pangolin ACE2 or human ACE2 natural variants reveals altered susceptibility to infection

2020 ◽  
Vol 101 (9) ◽  
pp. 921-924 ◽  
Author(s):  
Jingfang Wang ◽  
Xintian Xu ◽  
Xinbo Zhou ◽  
Ping Chen ◽  
Huiying Liang ◽  
...  
Keyword(s):  
Free Energy ◽  
Protein Binding ◽  
Binding Affinity ◽  
Binding Free Energy ◽  
Virus Transmission ◽  
Dynamics Simulation ◽  
Spike Protein ◽  
Susceptibility To Infection ◽  
Natural Variants ◽  
Complex Models

We constructed complex models of SARS-CoV-2 spike protein binding to pangolin or human ACE2, the receptor for virus transmission, and estimated the binding free energy changes using molecular dynamics simulation. SARS-CoV-2 can bind to both pangolin and human ACE2, but has a significantly lower binding affinity for pangolin ACE2 due to the increased binding free energy (9.5 kcal mol−1). Human ACE2 is among the most polymorphous genes, for which we identified 317 missense single-nucleotide variations (SNVs) from the dbSNP database. Three SNVs, E329G (rs143936283), M82I (rs267606406) and K26R (rs4646116), had a significant reduction in binding free energy, which indicated higher binding affinity than wild-type ACE2 and greater susceptibility to SARS-CoV-2 infection for people with them. Three other SNVs, D355N (rs961360700), E37K (rs146676783) and I21T (rs1244687367), had a significant increase in binding free energy, which indicated lower binding affinity and reduced susceptibility to SARS-CoV-2 infection.

scholarly journals SAMBE: The New Webserver for Predicting the Effect of nssNP on the Protein-Protein Binding Free Energy

2015 ◽  
Vol 108 (2) ◽  
pp. 157a-158a
Author(s):  
Marharyta Petukh ◽  
Jacon Morrison ◽  
Minghui Li ◽  
Anna Panchenko ◽  
Emil Alexov
Keyword(s):  
Free Energy ◽  
Protein Binding ◽  
Binding Free Energy

scholarly journals CHARMM-GUI Free Energy Calculator for Absolute and Relative Ligand Solvation and Binding Free Energy Simulations

2020 ◽  
Vol 16 (11) ◽  
pp. 7207-7218 ◽  
Author(s):  
Seonghoon Kim ◽  
Hiraku Oshima ◽  
Han Zhang ◽  
Nathan R. Kern ◽  
Suyong Re ◽  
...  
Keyword(s):  
Free Energy ◽  
Binding Free Energy ◽  
Energy Simulations
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