Talk:2010 Workshop on Free Energy Methods in Drug Design

Talk schedule planning

25 minutes

William Jorgensen (Yale) - Successes and Challenges for FEP-Guided Optimization of Enzyme Inhibitors

10 minutes

Julien Michel (Yale) - Water in binding free energy calculations

Talk titles and abstract

William Jorgensen, Yale University

Successes and Challenges for FEP-Guided Optimization of Enzyme Inhibitors

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Julien Michel, Yale University

Water in binding free energy calculations

The binding of a ligand to a protein generally occurs in aqueous solution and water profoundly influences the nature and energetics of protein-ligand interactions. Computer models that simulate ligand binding must correctly capture the influence of water to represent protein-ligand interactions accurately.

I will present popular strategies to model water in the context of binding free energy calculations, ranging from simple implicit solvent models to detailed explicit solvent models. For each approach I will discuss strengths, pitfalls and possible solutions. I will conclude with an outline of the challenges that remain to be addressed to model solvation in ligand binding using free energy methods.

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