Characterizing hydration sites in protein-ligand complexes towards the design of novel ligands

Hans Matter; Stefan Güssregen

doi:10.1016/j.bmcl.2018.05.061

Characterizing hydration sites in protein-ligand complexes towards the design of novel ligands

Bioorg Med Chem Lett. 2018 Aug 1;28(14):2343-2352. doi: 10.1016/j.bmcl.2018.05.061. Epub 2018 Jun 1.

Authors

Hans Matter¹, Stefan Güssregen²

Affiliations

¹ Sanofi-Aventis Deutschland GmbH, Integrated Drug Discovery (IDD), Synthetic Molecular Design, Building G838, Industriepark Höchst, 65926 Frankfurt am Main, Germany. Electronic address: Hans.Matter@sanofi.com.
² Sanofi-Aventis Deutschland GmbH, Integrated Drug Discovery (IDD), Synthetic Molecular Design, Building G838, Industriepark Höchst, 65926 Frankfurt am Main, Germany.

PMID: 29880400
DOI: 10.1016/j.bmcl.2018.05.061

Abstract

Water is an essential part of protein binding sites and mediates interactions to ligands. Its displacement by ligand parts affects the free binding energy of resulting protein-ligand complexes. Therefore the characterization of solvation properties is important for design. Of particular interest is the propensity of localized water to be favorably displaced by a ligand. This review discusses two popular computational approaches addressing these questions, namely WaterMap based on statistical mechanics analysis of MD simulations and 3D RISM based on integral equation theory of liquids. The theoretical background and recent applications in structure-based design will be presented.

Keywords: 3D RISM; Computer-aided drug design; Hydration sites; Structure-based design; WaterMap.

Publication types

Review

MeSH terms

Binding Sites
Drug Design*
Humans
Ligands
Molecular Dynamics Simulation
Proteins / chemistry*
Solubility

Substances

Ligands
Proteins