A molecular reconstruction approach to sitebased 3D-RISM and comparison to GIST hydration thermodynamic maps in an enzyme active site

Authors

Crystal Nguyen, University of California - San Diego
Takeshi Yamazaki, Vancouver Prostate Centre
Andriy Kovalenko, National Research Council of Canada
David A. Case, CUNY Lehman College
Michael K. Gilson, University of California San Diego
Tom Kurtzman, Rutgers University
Tyler Luchko, California State University, Northridge

Document Type

Article

Publication Date

7-10-2019

Abstract

Computed, high-resolution, spatial distributions of solvation energy and entropy can provide detailed information about the role of water in molecular recognition. While grid inhomogeneous solvation theory (GIST) provides rigorous, detailed thermodynamic information from explicit solvent molecular dynamics simulations, recent developments in the 3D reference interaction site model (3D-RISM) theory allow many of the same quantities to be calculated in a fraction of the time. However, 3D-RISM produces atomic-site, rather than molecular, density distributions, which are difficult to extract physical meaning from. To overcome this difficulty, we introduce a method to reconstruct molecular density distributions from atomic site density distributions. Furthermore, we assess the quality of the resulting solvation thermodynamics density distributions by analyzing the binding site of coagulation Factor Xa with both GIST and 3D-RISM. We find good qualitative agreement between the methods for oxygen and hydrogen densities as well as direct solute-solvent energetic interactions. However, 3D-RISM predicts lower energetic and entropic penalties for moving water from the bulk to the binding site.

Comments

This work was originally published in PLOS ONE, available at https://doi.org/10.1371/journal.pone.0219473

This article is distributed under the terms and conditions of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/