Implicit Solvents for the Polarizable Atomic Multipole AMOEBA Force Field

Computational protein design, ab initio protein/RNA folding, and protein–ligand screening can be too computationally demanding for explicit treatment of solvent. For these applications, implicit solvent offers a compelling alternative, which we describe here for the polarizable atomic multipole AMOE...

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Veröffentlicht in:Journal of chemical theory and computation 2021-04, Vol.17 (4), p.2323-2341
Hauptverfasser: Corrigan, Rae A, Qi, Guowei, Thiel, Andrew C, Lynn, Jack R, Walker, Brandon D, Casavant, Thomas L, Lagardere, Louis, Piquemal, Jean-Philip, Ponder, Jay W, Ren, Pengyu, Schnieders, Michael J
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Sprache:eng
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Zusammenfassung:Computational protein design, ab initio protein/RNA folding, and protein–ligand screening can be too computationally demanding for explicit treatment of solvent. For these applications, implicit solvent offers a compelling alternative, which we describe here for the polarizable atomic multipole AMOEBA force field based on three treatments of continuum electrostatics: numerical solutions to the nonlinear and linearized versions of the Poisson–Boltzmann equation (PBE), the domain-decomposition conductor-like screening model (ddCOSMO) approximation to the PBE, and the analytic generalized Kirkwood (GK) approximation. The continuum electrostatics models are combined with a nonpolar estimator based on novel cavitation and dispersion terms. Electrostatic model parameters are numerically optimized using a least-squares style target function based on a library of 103 small-molecule solvation free energy differences. Mean signed errors for the adaptive Poisson–Boltzmann solver (APBS), ddCOSMO, and GK models are 0.05, 0.00, and 0.00 kcal/mol, respectively, while the mean unsigned errors are 0.70, 0.63, and 0.58 kcal/mol, respectively. Validation of the electrostatic response of the resulting implicit solvents, which are available in the Tinker (or Tinker-HP), OpenMM, and Force Field X software packages, is based on comparisons to explicit solvent simulations for a series of proteins and nucleic acids. Overall, the emergence of performative implicit solvent models for polarizable force fields opens the door to their use for folding and design applications.
ISSN:1549-9618
1549-9626
DOI:10.1021/acs.jctc.0c01286