TY - JOUR
T1 - Implicit Solvents for the Polarizable Atomic Multipole AMOEBA Force Field
AU - Corrigan, Rae A.
AU - Qi, Guowei
AU - Thiel, Andrew C.
AU - Lynn, Jack R.
AU - Walker, Brandon D.
AU - Casavant, Thomas L.
AU - Lagardere, Louis
AU - Piquemal, Jean Philip
AU - Ponder, Jay W.
AU - Ren, Pengyu
AU - Schnieders, Michael J.
N1 - Funding Information:
All computations were performed on The University of Iowa Argon cluster with support and guidance from Danny Tang, Joe Hetrick, Glenn Johnson, and John Saxton. M.J.S. was supported by NIH R01DK110023, NIH R01DC012049, the Donald D. Harrington Fellows Program and NSF CHE-1751688. J.W.P. and P.R. were supported by R01GM106137 and R01GM114237. J.-P.P. and L.L. were supported by the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Program No 810367. R.A.C. and A.C.T. were supported by the NSF Graduate Research Fellowship Program NSF DGE-1945994, and G.Q. was supported by the Goldwater Foundation and the Iowa Center for Research by Undergraduates (ICRU).
Publisher Copyright:
© 2021 The Authors. Published by American Chemical Society.
PY - 2021/4/13
Y1 - 2021/4/13
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85104276654&partnerID=8YFLogxK
U2 - 10.1021/acs.jctc.0c01286
DO - 10.1021/acs.jctc.0c01286
M3 - Article
C2 - 33769814
AN - SCOPUS:85104276654
SN - 1549-9618
VL - 17
SP - 2323
EP - 2341
JO - Journal of Chemical Theory and Computation
JF - Journal of Chemical Theory and Computation
IS - 4
ER -