TY - JOUR
T1 - A generalized Kirkwood implicit solvent for the polarizable AMOEBA protein model
AU - Corrigan, Rae A.
AU - Thiel, Andrew C.
AU - Lynn, Jack R.
AU - Casavant, Thomas L.
AU - Ren, Pengyu
AU - Ponder, Jay W.
AU - Schnieders, Michael J.
N1 - Publisher Copyright:
© 2023 Author(s).
PY - 2023/8/7
Y1 - 2023/8/7
N2 - Computational simulation of biomolecules can provide important insights into protein design, protein-ligand binding interactions, and ab initio biomolecular folding, among other applications. Accurate treatment of the solvent environment is essential in such applications, but the use of explicit solvents can add considerable cost. Implicit treatment of solvent effects using a dielectric continuum model is an attractive alternative to explicit solvation since it is able to describe solvation effects without the inclusion of solvent degrees of freedom. Previously, we described the development and parameterization of implicit solvent models for small molecules. Here, we extend the parameterization of the generalized Kirkwood (GK) implicit solvent model for use with biomolecules described by the AMOEBA force field via the addition of corrections to the calculation of effective radii that account for interstitial spaces that arise within biomolecules. These include element-specific pairwise descreening scale factors, a short-range neck contribution to describe the solvent-excluded space between pairs of nearby atoms, and finally tanh-based rescaling of the overall descreening integral. We then apply the AMOEBA/GK implicit solvent to a set of ten proteins and achieve an average coordinate root mean square deviation for the experimental structures of 2.0 Å across 500 ns simulations. Overall, the continued development of implicit solvent models will help facilitate the simulation of biomolecules on mechanistically relevant timescales.
AB - Computational simulation of biomolecules can provide important insights into protein design, protein-ligand binding interactions, and ab initio biomolecular folding, among other applications. Accurate treatment of the solvent environment is essential in such applications, but the use of explicit solvents can add considerable cost. Implicit treatment of solvent effects using a dielectric continuum model is an attractive alternative to explicit solvation since it is able to describe solvation effects without the inclusion of solvent degrees of freedom. Previously, we described the development and parameterization of implicit solvent models for small molecules. Here, we extend the parameterization of the generalized Kirkwood (GK) implicit solvent model for use with biomolecules described by the AMOEBA force field via the addition of corrections to the calculation of effective radii that account for interstitial spaces that arise within biomolecules. These include element-specific pairwise descreening scale factors, a short-range neck contribution to describe the solvent-excluded space between pairs of nearby atoms, and finally tanh-based rescaling of the overall descreening integral. We then apply the AMOEBA/GK implicit solvent to a set of ten proteins and achieve an average coordinate root mean square deviation for the experimental structures of 2.0 Å across 500 ns simulations. Overall, the continued development of implicit solvent models will help facilitate the simulation of biomolecules on mechanistically relevant timescales.
UR - http://www.scopus.com/inward/record.url?scp=85166396462&partnerID=8YFLogxK
U2 - 10.1063/5.0158914
DO - 10.1063/5.0158914
M3 - Article
C2 - 37526158
AN - SCOPUS:85166396462
SN - 0021-9606
VL - 159
JO - Journal of Chemical Physics
JF - Journal of Chemical Physics
IS - 5
M1 - 054102
ER -