Hydration Free Energies of Polypeptides from Popular Implicit Solvent Models versus All-Atom Simulation Results Based on Molecular Quasichemical Theory

Adhikari, Rohan S.; Valiya Parambathu, Arjun; Chapman, Walter G.; Asthagiri, Dilipkumar N.

doi:10.1021/acs.jpcb.2c05725

Title: Hydration Free Energies of Polypeptides from Popular Implicit Solvent Models versus All-Atom Simulation Results Based on Molecular Quasichemical Theory

Journal Article · Thu Nov 10 00:00:00 EST 2022 · Journal of Physical Chemistry. B

DOI:https://doi.org/10.1021/acs.jpcb.2c05725· OSTI ID:1898978

Adhikari, Rohan S. ^[1]; Valiya Parambathu, Arjun ^[2]; Chapman, Walter G. ^[1];

^[3]

Rice Univ., Houston, TX (United States)
Univ. of Delaware, Newark, DE (United States)
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

Calculating the hydration free energy of a macromolecule in all-atom simulations has long remained a challenge, necessitating the use of models wherein the effect of the solvent is captured without explicit account of solvent degrees of freedom. This situation has changed with developments in the molecular quasi-chemical theory (QCT)-an approach that enables calculation of the hydration free energy of macromolecules within all-atom simulations at the same resolution as is possible for small molecular solutes. The theory also provides a rigorous and physically transparent framework to conceptualize and model interactions in molecular solutions and thus provides a convenient framework to investigate the assumptions in implicit solvent models. In this study, we compare the results using molecular QCT versus predictions from EEF1, ABSINTH, and GB/SA implicit solvent models for polyglycine and polyalanine solutes covering a range of chain lengths and conformations. The hydration free energies or the differences in hydration free energies between conformers obtained from the implicit solvent models do not agree with explicit solvent results, with the deviations being largest for the group additive EEF1 and ABSINTH models. GB/SA does better in capturing the qualitative trends seen in explicit solvent results. Finally, analysis founded on QCT reveals the critical importance of the cooperativity of hydration that is inherent in the hydrophilic and hydrophobic contributions to hydration-physics that is not well captured in additive models but somewhat better accounted for by means of a dielectric in the GB/SA approach.

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Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC)

Sponsoring Organization:: USDOE; Robert A. Welch Foundation

Grant/Contract Number:: AC05-00OR22725; C-1241; AC02-05CH11231

OSTI ID:: 1898978

Journal Information:: Journal of Physical Chemistry. B, Vol. 126, Issue 46; ISSN 1520-6106

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: English

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
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Title: Hydration Free Energies of Polypeptides from Popular Implicit Solvent Models versus All-Atom Simulation Results Based on Molecular Quasichemical Theory

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