Comparison of RESP and IPolQ-Mod Partial Charges for Solvation Free Energy Calculations of Various Solute/Solvent Pairs

2017 ◽  
Vol 13 (12) ◽  
pp. 6266-6274 ◽  
Author(s):  
Andreas Mecklenfeld ◽  
Gabriele Raabe
Keyword(s):  
Free Energy ◽  
Solvation Free Energy ◽  
Free Energy Calculations ◽  
Energy Calculations ◽  
Partial Charges

Performing solvation free energy calculations in LAMMPS using the decoupling approach

2020 ◽  
Vol 34 (6) ◽  
pp. 641-646
Author(s):  
Vikram Khanna ◽  
Jacob I. Monroe ◽  
Michael F. Doherty ◽  
Baron Peters
Keyword(s):  
Free Energy ◽  
Solvation Free Energy ◽  
Free Energy Calculations ◽  
Energy Calculations ◽  
Decoupling Approach

Alchemical Hydration Free Energy Calculations Using Molecular Dynamics with Explicit Polarization and Induced Polarity Decoupling: An On-the-Fly Approach

2020 ◽  
Author(s):  
Braden Kelly ◽  
William Smith
Keyword(s):  
Free Energy ◽  
Gas Phase ◽  
Free Energy Calculations ◽  
Partial Charge ◽  
Average Absolute Deviation ◽  
Absolute Deviation ◽  
Energy Calculations ◽  
Lennard Jones ◽  
Partial Charges ◽  
The Cost

<div>We present a methodology using fixed charge force-fields for alchemical solvation free energy calculations which accounts for the change in polarity that the solute experiences as it transfers from the gas-phase to the condensed phase. We update partial charges using QM/MM snapshots, decoupling the electric field appropriately when updating the partial charges. We also show how to account for the cost of self-polarization. We test our methodology on 30 molecules ranging from small polar to large drug-like molecules. We use Minimum Basis Iterative Stockholder (MBIS), Restrained Electrostatic Potential (RESP) and AM1-BCC partial charge methodologies. Using our method with MP2/cc-pVTZ and MBIS partial charges yields an Average Absolute Deviation (AAD) of 6.3 kJ·mol−1 in comparison with the AM1-BCC result of 8.6 kJ·mol−1. AM1-BCC is within experimental uncertainty on 10% of the data compared to 30% with our method. We conjecture that results can be further improved by using Lennard-Jones and torsional parameters refitted to MBIS and RESP partial charge methods that use high levels of theory.</div>

scholarly journals The SAMPL6 SAMPLing challenge: Assessing the reliability and efficiency of binding free energy calculations

2019 ◽  
Author(s):  
Andrea Rizzi ◽  
Travis Jensen ◽  
David R. Slochower ◽  
Matteo Aldeghi ◽  
Vytautas Gapsys ◽  
...  
Keyword(s):  
Free Energy ◽  
Convergence Rates ◽  
Binding Free Energy ◽  
Potential Of Mean Force ◽  
Free Energy Calculations ◽  
Energy Estimates ◽  
Initial Population ◽  
Energy Calculations ◽  
Partial Charges ◽  
Expanded Ensemble

AbstractApproaches for computing small molecule binding free energies based on molecular simulations are now regularly being employed by academic and industry practitioners to study receptor-ligand systems and prioritize the synthesis of small molecules for ligand design. Given the variety of methods and implementations available, it is natural to ask how the convergence rates and final predictions of these methods compare. In this study, we describe the concept and results for the SAMPL6 SAMPLing challenge, the first challenge from the SAMPL series focusing on the assessment of convergence properties and reproducibility of binding free energy methodologies. We provided parameter files, partial charges, and multiple initial geometries for two octa-acid (OA) and one cucurbit[8]uril (CB8) host-guest systems. Participants submitted binding free energy predictions as a function of the number of force and energy evaluations for seven different alchemical and physical-pathway (i.e., potential of mean force and weighted ensemble of trajectories) methodologies implemented with the GROMACS, AMBER, NAMD, or OpenMM simulation engines. To rank the methods, we developed an efficiency statistic based on bias and variance of the free energy estimates. For the two small OA binders, the free energy estimates computed with alchemical and potential of mean force approaches show relatively similar variance and bias as a function of the number of energy/force evaluations, with the attach-pull-release (APR), GROMACS expanded ensemble, and NAMD double decoupling submissions obtaining the greatest efficiency. The differences between the methods increase when analyzing the CB8-quinine system, where both the guest size and correlation times for system dynamics are greater. For this system, nonequilibrium switching (GROMACS/NS-DS/SB) obtained the overall highest efficiency. Surprisingly, the results suggest that specifying force field parameters and partial charges is insufficient to generally ensure reproducibility, and we observe differences between seemingly converged predictions ranging approximately from 0.3 to 1.0 kcal/mol, even with almost identical simulations parameters and system setup (e.g., Lennard-Jones cutoff, ionic composition). Further work will be required to completely identify the exact source of these discrepancies. Among the conclusions emerging from the data, we found that Hamiltonian replica exchange—while displaying very small variance—can be affected by a slowly-decaying bias that depends on the initial population of the replicas, that bidirectional estimators are significantly more efficient than unidirectional estimators for nonequilibrium free energy calculations for systems considered, and that the Berendsen barostat introduces non-negligible artifacts in expanded ensemble simulations.

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