Efficient consideration of coordinated water molecules improves computational protein-protein and protein-ligand docking [article]

Ryan E Pavlovicz, Hahnbeom Park, Frank DiMaio
2019 bioRxiv   pre-print
Highly-coordinated water molecules are frequently an integral part of protein- protein and protein-ligand interfaces. We introduce an updated energy model that efficiently captures the energetic effects of these highly-coordinated water molecules on the surfaces of proteins. A two-stage protocol is developed in which polar groups arranged in geometries suitable for water placement are first identified, then a modified Monte Carlo simulation allows highly coordinated waters to emerge. This
more » ... explicit" water model is implemented in Rosetta and allows for simultaneous prediction of side chain conformation and coordinated water geometry; the approach is suitable for structure prediction and protein design. We show that our new approach and energy model yield significant improvements in native structure recovery of protein-protein and protein-ligand docking.
doi:10.1101/618603 fatcat:jfxl2xhb4rhshmzy22drwyi4dy