Predicting induced fit in docking and loop prediction

Ruben Abagyan
Scripps College

Conformational changes induced by protein-protein or protein-small molecule associations, or receptor surface-peptide interactions present a major challenge in structure prodiction. Previously we demonstrated that a systematic refinement of trial protein-protein interfaces improves the discrimination between a near-native solution and other low-energy conformations. Recently we studied conformational flexibility

in ligand binding pockets of kinases and proposed a protocol for receptor-flexible docking leading to better pocket models. Using a similar protocol the rhodopsin pocket with distorted side-chains can be restored to its bound conformation by flexible docking of the retinal molecule. The backbone flexibility is the most difficult to predict and we studied ways to generate alternative backbone conformations by combinding low-resolution harmonic models with refined high resolution models. Finally we discuss a protocol for improved loop prediciton in homology modeling.

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