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bioRxiv · 10.1101/618603

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

Pavlovicz, R. E.·Park, H.·DiMaio, F.
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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 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 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.

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Pavlovicz, R. E., Park, H., DiMaio, F.. 2019-04-25. Efficient consideration of coordinated water molecules improves computational protein-protein and protein-ligand docking. https://doi.org/10.1101/618603

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