Comprehensive 3D-RISM Analysis of the Hydration of Small Molecule Binding Sites in Ligand-free Protein Structures

Overview

Journal J Comput Chem

Publisher Wiley

Specialties Biology
Chemistry

Date 2020 Aug 21

PMID 32815201

Citations 4

Authors

Takashi Yoshidome

Mitsunori Ikeguchi

Masateru Ohta

Affiliations

Soon will be listed here.

Abstract

Hydration is a critical factor in the ligand binding process. Herein, to examine the hydration states of ligand binding sites, the three-dimensional distribution function for the water oxygen site, g (r), is computed for 3,706 ligand-free protein structures based on the corresponding small molecule-protein complexes using the 3D-RISM theory. For crystallographic waters (CWs) close to the ligand, g (r) reveals that several CWs are stabilized by interaction networks formed between the ligand, CW, and protein. Based on the g (r) for the crystallographic binding pose of the ligand, hydrogen bond interactions are dominant in the highly hydrated regions while weak interactions such as CH-O are dominant in the moderately hydrated regions. The polar heteroatoms of the ligand occupy the highly hydrated and moderately hydrated regions in the crystallographic (correct) and wrongly docked (incorrect) poses, respectively. Thus, the g (r) of polar heteroatoms may be used to distinguish the correct binding poses.

Citing Articles

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Accurate Prediction of Hydration Sites of Proteins Using Energy Model With Atom Embedding.

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PMID: 34616774 PMC: 8488165. DOI: 10.3389/fmolb.2021.756075.

Comprehensive 3D-RISM analysis of the hydration of small molecule binding sites in ligand-free protein structures.

Yoshidome T, Ikeguchi M, Ohta M J Comput Chem. 2020; 41(28):2406-2419.

PMID: 32815201 PMC: 7540010. DOI: 10.1002/jcc.26406.

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