Journal ArticleDOI
End-Point Binding Free Energy Calculation with MM/PBSA and MM/GBSA: Strategies and Applications in Drug Design
TLDR
In this review, methods to adjust the polar solvation energy and to improve the performance of MM/PBSA and MM/GBSA calculations are reviewed and discussed and guidance is provided for practically applying these methods in drug design and related research fields.Abstract:
Molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) and molecular mechanics generalized Born surface area (MM/GBSA) are arguably very popular methods for binding free energy prediction since they are more accurate than most scoring functions of molecular docking and less computationally demanding than alchemical free energy methods. MM/PBSA and MM/GBSA have been widely used in biomolecular studies such as protein folding, protein-ligand binding, protein-protein interaction, etc. In this review, methods to adjust the polar solvation energy and to improve the performance of MM/PBSA and MM/GBSA calculations are reviewed and discussed. The latest applications of MM/GBSA and MM/PBSA in drug design are also presented. This review intends to provide readers with guidance for practically applying MM/PBSA and MM/GBSA in drug design and related research fields.read more
Citations
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Journal ArticleDOI
Fast Identification of Possible Drug Treatment of Coronavirus Disease -19 (COVID-19) Through Computational Drug Repurposing Study
TL;DR: The findings of this study can facilitate rational drug design targeting the SARS-CoV-2 main protease, including carfilzomib, eravacycline, valrubicin, lopinavir, and elbasvir.
Journal ArticleDOI
gmx_MMPBSA: A New Tool to Perform End-State Free Energy Calculations with GROMACS.
Mario S. Valdés-Tresanco,Mario E. Valdés-Tresanco,Pedro A. Valiente,Pedro A. Valiente,Ernesto Moreno +4 more
TL;DR: Gmx_MMPBSA as discussed by the authors is a new tool to perform end-state free energy calculations from GROMACS molecular dynamics trajectories, which provides the user with several options, including bounding free energy calculation with different solvation models (PB, GB, or 3D-RISM), stability calculations, computational alanine scanning, entropy corrections, and binding free energy decomposition.
Journal ArticleDOI
Targeting SARS-CoV-2 spike protein of COVID-19 with naturally occurring phytochemicals: an in silico study for drug development.
Preeti Pandey,Jitendra Subhash Rane,Aroni Chatterjee,Abhijeet Kumar,Rajni Khan,Amresh Prakash,Shashikant Ray +6 more
TL;DR: Molecular docking studies using 10 potential naturally occurring compounds against the SARS-CoV-2 spike protein and compared their affinity with an FDA approved repurposed drug hydroxychloroquine revealed that these molecules bind with the hACE2-S complex with low binding free energy, and ADME analysis suggested that they consist of drug-likeness property, which may be further explored as anti-SARS- CoV- 2 agents.
Journal ArticleDOI
A fast and high-quality charge model for the next generation general AMBER force field.
TL;DR: A new set of BCC parameters specifically for GAFF2 is developed using 442 neutral organic solutes covering diverse functional groups in aqueous solution and shows excellent performance in the solvation free energy (SFE) calculation on diverse solutes in various organic solvents across a range of different dielectric constants.
Journal ArticleDOI
Thermodynamics and Kinetics of Drug-Target Binding by Molecular Simulation.
TL;DR: To assess the present and future value of simulation for drug discovery, this work reviews key applications of advanced methods for sampling complex free-energy landscapes at near nonergodicity conditions and for estimating the rate coefficients of very slow processes of pharmacological interest.
References
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Garrett M. Morris,David S. Goodsell,Robert Scott Halliday,Ruth Huey,William E. Hart,Richard K. Belew,Arthur J. Olson +6 more
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TL;DR: The development, current features, and some directions for future development of the Amber package of computer programs, which contains a group of programs embodying a number of powerful tools of modern computational chemistry, focused on molecular dynamics and free energy calculations of proteins, nucleic acids, and carbohydrates.
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Electrostatics of nanosystems: Application to microtubules and the ribosome
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Calculating Structures and Free Energies of Complex Molecules: Combining Molecular Mechanics and Continuum Models
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TL;DR: A historical perspective on the application of molecular dynamics to biological macromolecules is presented and recent developments combining state-of-the-art force fields with continuum solvation calculations have allowed for the fourth era of MD applications in which one can often derive both accurate structure and accurate relative free energies from molecular dynamics trajectories.