Motifs for Molecular Recognition Exploiting Hydrophobic Enclosure in Protein-ligand Binding

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2007 Jan 6

PMID 17204562

Citations 259

Authors

Tom Young

Robert Abel

Byungchan Kim

Bruce J Berne

Richard A Friesner

Affiliations

Soon will be listed here.

Abstract

The thermodynamic properties and phase behavior of water in confined regions can vary significantly from that observed in the bulk. This is particularly true for systems in which the confinement is on the molecular-length scale. In this study, we use molecular dynamics simulations and a powerful solvent analysis technique based on inhomogenous solvation theory to investigate the properties of water molecules that solvate the confined regions of protein active sites. Our simulations and analysis indicate that the solvation of protein active sites that are characterized by hydrophobic enclosure and correlated hydrogen bonds induce atypical entropic and enthalpic penalties of hydration. These penalties apparently stabilize the protein-ligand complex with respect to the independently solvated ligand and protein, which leads to enhanced binding affinities. Our analysis elucidates several challenging cases, including the super affinity of the streptavidin-biotin system.

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