Abstract
We present a novel web server, named gridSolvate, dedicated to the prediction of biomolecular hydration properties. Given a solute in atomic representation, such as a protein or protein–ligand complex, the server determines positions and excess chemical potential of buried and first hydration shell water molecules. Calculations are based on our semiexplicit hydration model that provides computational efficiency close to implicit solvent approaches, yet captures a number of physical effects unique to explicit solvent representation. The model was introduced and validated before in the context of bulk hydration of drug-like solutes and determination of protein hydration sites. Current methodological developments merge those two avenues into a single, easily accessible tool. Here, we focus on the server’s ability to predict water distribution and affinity within protein–ligand interfaces. We demonstrate that with possibly minimal user intervention the server correctly predicts the locations of 77% of interface water molecules in an external set of test structures. The server is freely available at https://gsolvate.biomod.cent.uw.edu.pl.
Highlights
The interplay between the aqueous environment and living matter has been actively studied for decades.[1]
A wide array of available approaches starts with explicit solvent simulations typically combined with various postprocessing techniques aimed at general description of solvent thermodynamic properties,[4,5] estimation of water binding free energy to specific sites,[6,7] bound water detection,[8] or scoring.[9−11] Computationally less demanding, yet less accurate, are implicit solvent models.[12]
The calculations are much faster than explicit solvent simulations, yet still capture a number of physical effects that are neglected in typical simplified approaches: directionality of water hydrogen bonds, entropic penalty due to limited rotational freedom of bound water, or the asymmetry of charge distribution within water molecule
Summary
The interplay between the aqueous environment and living matter has been actively studied for decades.[1]. We developed a semiexplicit solvent model, applicable to biological macromolecules (proteins, nucleic acids), drug-like compounds, and their complexes,[27−29] that provides information concerning locations of buried and first hydration shell water molecules together with estimates of their excess chemical potentials. We direct the reader to our previous reports concerning theoretical model assumptions,[27] estimation of hydration free energies of drug-like compounds,[28] and prediction of protein internal hydration sites.[29] Here, we present a gridSolvate web server that allows automatized calculations for protein−ligand complexes and makes the method available for external users
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