Journal article
A generalized Kirkwood implicit solvent for the polarizable AMOEBA protein model
The Journal of chemical physics, Vol.159(5), 054102
08/07/2023
DOI: 10.1063/5.0158914
PMCID: PMC10396400
PMID: 37526158
Abstract
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.
Details
- Title: Subtitle
- A generalized Kirkwood implicit solvent for the polarizable AMOEBA protein model
- Creators
- Rae A. Corrigan - University of IowaAndrew C. Thiel - University of IowaJack R. Lynn - University of IowaThomas L. Casavant - Department of Electrical and Computer Engineering, The University of IowaPengyu Ren - Department of Biomedical Engineering, The University of Texas in AustinJay W. Ponder - Washington University in St. LouisMichael J. Schnieders - 5Department of Biochemistry and Molecular Biology, The University of Iowa, Iowa City, Iowa 52242, USA
- Resource Type
- Journal article
- Publication Details
- The Journal of chemical physics, Vol.159(5), 054102
- DOI
- 10.1063/5.0158914
- PMID
- 37526158
- PMCID
- PMC10396400
- ISSN
- 0021-9606
- eISSN
- 1089-7690
- Number of pages
- 16
- Grant note
- CHE-1751688; 000390183 / National Science Foundation (https://doi.org/10.13039/100000001) R01DC012049 / National Institute on Deafness and Other Communication Disorders (https://doi.org/10.13039/100000055) R01GM114237; R01GM106137 / National Institute of General Medical Sciences (https://doi.org/10.13039/100000057)
- Language
- English
- Date published
- 08/07/2023
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Electrical and Computer Engineering; Iowa Technology Institute; Biochemistry and Molecular Biology; Chemical and Biochemical Engineering
- Record Identifier
- 9984448057202771
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