Preparation and refinement of model protein-ligand complexes.

The formation of ligand-protein complexes are critical for the correct functioning of a cell. The prediction of these interactions is important for our understanding of how the cell works and for the development of new drug molecules. Homology modeling is a method for predicting the structure of a protein based on a crystal structure template. Once a model of the protein is complete, a ligand-docking algorithm predicts the ligand-protein model interaction by searching for the best steric and energetically favorable fit. A refinement of the ligand-binding pocket improves the predicted interactions by considering the flexible nature of the ligand-binding pocket. In this chapter, we describe, from first principles, methods to identify and prepare the ligand-binding pocket in a protein model, to dock the ligand, and refine the resulting complex.