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Thermodynamic Decomposition of Solvation Free Energies with Particle Mesh Ewald and Long-Range Lennard-Jones Interactions in Grid Inhomogeneous Solvation Theory

preprint
revised on 17.11.2020, 05:06 and posted on 17.11.2020, 09:55 by Lieyang Chen, Anthony Cruz, Daniel R. Roe, Andrew Simmonett, Lauren Wickstrom, Nanjie Deng, Tom Kurtzman
Grid Inhomogeneous Solvation Theory (GIST) maps out solvation thermodynamic properties on a fine meshed grid and provides a statistical mechanical formalism for thermodynamic end-state calculations. However, differences in how long-range non-bonded interactions are calculated in molecular dynamics engines and in the current implementation of GIST have prevented precise comparisons between free energies estimated using GIST and those from other free energy methods such as thermodynamic integration (TI). Here, we address this by presenting PME-GIST, a formalism by which particle mesh Ewald (PME) based electrostatic energies and long-range Lennard-Jones (LJ) energies are decomposed and assigned to individual atoms and the corresponding voxels they occupy in a manner consistent with the GIST approach. PME-GIST yields potential energy calculations that are precisely consistent with modern simulation engines and performs these calculations at a dramatically faster speed than prior implementations. Here, we apply PME-GIST end-states analyses to 32 small molecules whose solvation free energies are close to evenly distributed from 2 kcal/mol to -17 kcal/mol and obtain solvation energies consistent with TI calculations (R2 = 0.99, mean unsigned difference 0.8 kcal/mol). We also estimate the entropy contribution from the 2nd and higher order entropy terms that are truncated in GIST by the differences between entropies calculated in TI and GIST. With a simple correction for the high order entropy terms, PME-GIST obtains solvation free energies that are highly consistent with TI calculations (R2 = 0.99, mean unsigned difference = 0.4 kcal/mol) and experimental results (R2 = 0.88, mean unsigned difference = 1.4 kcal/mol). The precision of PME-GIST also enables us to show that the solvation free energy of small hydrophobic and hydrophilic molecules can be largely understood based on perturbations of the solvent in a region extending a few solvation shells from the solute. We have integrated PME-GIST into the open-source molecular dynamics analysis software CPPTRAJ.

Funding

NIH R01-GM100946.

History

Email Address of Submitting Author

simpleliquid@gmail.com

Institution

Ph.D. Programs in Chemistry & Biochemistry, The Graduate Center of the the City University of NY

Country

USA

ORCID For Submitting Author

0000-0003-0900-772X

Declaration of Conflict of Interest

No Conflicts of Interest

Version Notes

Fixed mislabeled axis labels on figure 5 (switched x and y axis labels so they are now correct). Fixed inaccurate citations.

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