Paper Info
Title
Efficient consideration of coordinated water molecules improves computational protein-protein and protein-ligand docking discrimination.
Abstract
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 ordered water molecules on the surfaces of proteins. A two-stage method 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 be placed on the surface of a protein while simultaneously sampling amino acid side chain orientations. This "semi-explicit" water model is implemented in Rosetta and is suitable for both 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 discrimination tests. Author summary Well-coordinated water molecules-those forming multiple hydrogen bonds with nearby polar groups-play an important role in the structure of biomolecular systems, yet the effect of these waters is often not considered in molecular energy computations. In this paper, we describe a method to efficiently consider these water molecules both implicitly and explicitly at the interfaces formed by two polar molecules. In computations related to determining how a protein interacts with binding partners, we show that the use of this new method significantly improves results. Future application of this approach may improve the design of new protein and small molecule drugs.
Year
DOI
Venue
2020
10.1371/journal.pcbi.1008103
PLOS COMPUTATIONAL BIOLOGY
DocType
Volume
Issue
Journal
16
9
ISSN
Citations 
PageRank 
1553-734X
0
0.34
References 
Authors
0
3
Name
Order
Citations
PageRank
Ryan E Pavlovicz100.34
Hahnbeom Park2525.17
Frank DiMaio3656.98