Accurately modeling the binding of proteins with small molecules – a key challenge in structure-based drug-design -- requires the ability to accurately model the water in and around the two solutes. This can be challenging, as water adopts intricate structures in protein binding sites prior to binding, and, in the bound complex, water molecules can occupy buried sites, where they bridge between the protein and the ligand. Accounting for the effects of water in these complex environments poses a number of challenges. For example, it is not a given that a water model that does a good job of replicating the properties of homogeneous, bulk water will work equally well in the ordering environment of a binding site. In addition, simulations that effectively sample water at the protein surface may not account for the slow exchange of water in buried sites. And protein-ligand docking calculations are sensitive to the treatment of crystallographic waters. Here, I will discuss collaborative efforts to address a number of these issues and thereby advance our ability to model and predict protein-ligand binding.

Modeling water in molecular recognition and drug design

2019 Fall National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.