Rapid Alchemical Free Energy Calculation Employing a Generalized Born Implicit Solvent Model

2014 ◽  
Vol 119 (3) ◽  
pp. 968-975 ◽  
Author(s):  
Katja Ostermeir ◽  
Martin Zacharias
Keyword(s):  
Free Energy ◽  
Free Energy Calculation ◽  
Implicit Solvent ◽  
Energy Calculation ◽  
Generalized Born ◽  
Implicit Solvent Model ◽  
Solvent Model ◽  
Alchemical Free Energy

scholarly journals Effect of Atomic Charges on Octanol–Water Partition Coefficient Using Alchemical Free Energy Calculation

Molecules ◽  
2018 ◽  
Vol 23 (2) ◽  
pp. 425 ◽  
Author(s):  
Koji Ogata ◽  
Makoto Hatakeyama ◽  
Shinichiro Nakamura
Keyword(s):  
Free Energy ◽  
Partition Coefficient ◽  
Free Energy Calculation ◽  
Energy Calculation ◽  
Atomic Charges ◽  
Water Partition Coefficient ◽  
Alchemical Free Energy

scholarly journals Evaluation of Hydration Free Energy by Level-Set Variational Implicit-Solvent Model with Coulomb-Field Approximation

2013 ◽  
Vol 9 (3) ◽  
pp. 1778-1787 ◽  
Author(s):  
Zuojun Guo ◽  
Bo Li ◽  
Joachim Dzubiella ◽  
Li-Tien Cheng ◽  
J. Andrew McCammon ◽  
...  
Keyword(s):  
Free Energy ◽  
Level Set ◽  
Coulomb Field ◽  
Field Approximation ◽  
Implicit Solvent ◽  
Hydration Free Energy ◽  
Implicit Solvent Model ◽  
Solvent Model

scholarly journals An Effective MM/GBSA Protocol for Absolute Binding Free Energy Calculations: A Case Study on SARS-CoV-2 Spike Protein and the Human ACE2 Receptor

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2383
Author(s):  
Negin Forouzesh ◽  
Nikita Mishra
Keyword(s):  
Free Energy ◽  
Binding Free Energy ◽  
Normal Mode Analysis ◽  
Free Energy Calculations ◽  
Spike Protein ◽  
Upper And Lower Bounds ◽  
Mode Analysis ◽  
Implicit Solvent ◽  
Energy Calculation ◽  
Generalized Born

The binding free energy calculation of protein–ligand complexes is necessary for research into virus–host interactions and the relevant applications in drug discovery. However, many current computational methods of such calculations are either inefficient or inaccurate in practice. Utilizing implicit solvent models in the molecular mechanics generalized Born surface area (MM/GBSA) framework allows for efficient calculations without significant loss of accuracy. Here, GBNSR6, a new flavor of the generalized Born model, is employed in the MM/GBSA framework for measuring the binding affinity between SARS-CoV-2 spike protein and the human ACE2 receptor. A computational protocol is developed based on the widely studied Ras–Raf complex, which has similar binding free energy to SARS-CoV-2/ACE2. Two options for representing the dielectric boundary of the complexes are evaluated: one based on the standard Bondi radii and the other based on a newly developed set of atomic radii (OPT1), optimized specifically for protein–ligand binding. Predictions based on the two radii sets provide upper and lower bounds on the experimental references: −14.7(ΔGbindBondi)<−10.6(ΔGbindExp.)<−4.1(ΔGbindOPT1) kcal/mol. The consensus estimates of the two bounds show quantitative agreement with the experiment values. This work also presents a novel truncation method and computational strategies for efficient entropy calculations with normal mode analysis. Interestingly, it is observed that a significant decrease in the number of snapshots does not affect the accuracy of entropy calculation, while it does lower computation time appreciably. The proposed MM/GBSA protocol can be used to study the binding mechanism of new variants of SARS-CoV-2, as well as other relevant structures.

scholarly journals Implementation of the QUBE Force Field for High-Throughput Alchemical Free Energy Calculations

2020 ◽  
Author(s):  
Lauren Nelson ◽  
Sofia Bariami ◽  
Chris Ringrose ◽  
Joshua Horton ◽  
Vadiraj Kurdekar ◽  
...  
Keyword(s):  
Free Energy ◽  
Force Field ◽  
High Throughput ◽  
Potential Energy Function ◽  
Free Energy Calculations ◽  
Dynamics Simulation ◽  
Free Energy Calculation ◽  
Energy Calculation ◽  
Alchemical Free Energy ◽  
Simulation Package

<div><div><div><p>The quantum mechanical bespoke (QUBE) force field approach has been developed to facilitate the automated derivation of potential energy function parameters for modelling protein-ligand binding. To date the approach has been validated in the context of Monte Carlo simulations of protein-ligand complexes. We describe here the implementation of the QUBE force field in the alchemical free energy calculation molecular dynamics simulation package SOMD. The implementation is validated by computing relative binding free energies for two congeneric series of non-nucleoside inhibitors of HIV-1 reverse transcriptase using QUBE and AMBER/GAFF force fields. The availability of QUBE in a modern simulation package that makes efficient use of GPU acceleration will greatly facilitate future high-throughput alchemical free energy calculation studies.</p></div></div></div>

Parameterization of the hydration free energy computations for organic solutes in the framework of the implicit solvent model with the nonuniform dielectric function

2013 ◽  
Vol 1009 ◽  
pp. 50-54
Author(s):  
Fedor Grigoriev ◽  
Mikhail Basilevsky ◽  
Leonid Gorb ◽  
Olha O. Brovarets ◽  
Alina Fedorenko ◽  
...  
Keyword(s):  
Free Energy ◽  
Dielectric Function ◽  
Implicit Solvent ◽  
Organic Solutes ◽  
Hydration Free Energy ◽  
Implicit Solvent Model ◽  
Solvent Model

scholarly journals Effect of set up protocols on the accuracy of alchemical free energy calculation over a set of ACK1 inhibitors

PLoS ONE ◽  
2019 ◽  
Vol 14 (3) ◽  
pp. e0213217 ◽  
Author(s):  
José M. Granadino-Roldán ◽  
Antonia S. J. S. Mey ◽  
Juan J. Pérez González ◽  
Stefano Bosisio ◽  
Jaime Rubio-Martinez ◽  
...  
Keyword(s):  
Free Energy ◽  
Free Energy Calculation ◽  
Energy Calculation ◽  
Set Up ◽  
Alchemical Free Energy

scholarly journals Synergistic approach to improve “alchemical” free energy calculation in rugged energy surface

2007 ◽  
Vol 126 (14) ◽  
pp. 144109 ◽  
Author(s):  
Donghong Min ◽  
Hongzhi Li ◽  
Guohui Li ◽  
Ryan Bitetti-Putzer ◽  
Wei Yang
Keyword(s):  
Free Energy ◽  
Energy Surface ◽  
Free Energy Calculation ◽  
Energy Calculation ◽  
Synergistic Approach ◽  
Alchemical Free Energy
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