GalaxyWater-wKGB: Prediction of Water Positions on Protein Structure Using wKGB Statistical Potential.

Abstract

Proteins fold and function in water, and protein-water interactions play important roles in protein structure and function. In computational studies on protein structure and interaction, the effect of water is considered either implicitly or explicitly. Implicit water models are frequently used in protein structure prediction and docking because they are computationally much more efficient than explicit water models, which are often employed in molecular dynamics (MD) simulations. However, implicit water models that treat water as a continuous solvent medium cannot account for specific atomistic protein-water interactions that are critical for structure formation and interactions with other molecules. Various methods for predicting water molecules that form specific atomistic interactions with proteins have been developed. Methods involving MD simulations or the integral equation theory tend to produce more accurate results at a higher computational cost than simple geometry- or energy-based methods. Here, we present a novel method for predicting water positions on a protein surface called GalaxyWater-wKGB, which is based on a statistical potential, a water knowledge-based potential based on the generalized Born model (wKGB). This method is accurate and rapid because it does not require conformational sampling or iterative computation owing to the effective statistical treatment employed to derive the potential. The statistical potential describes specific protein atom-water interactions more accurately than conventional potentials by considering the dependence on the degree of solvent accessibility of protein atoms as well as on protein atom-water distances and orientations. The introduction of solvent accessibility allows effective consideration of competing nonspecific protein-water and intraprotein interactions. When tested on high-resolution protein crystal structures, this method could recover similar or larger fractions of crystallographic water 180 times faster than the sophisticated integral equation theory, 3D-RISM. A web service of this water prediction method is freely available at http://galaxy.seoklab.org/wkgb.