Protein-peptide molecular docking with large-scale conformational changes: the p53-MDM2 interaction.

ABSTRACT: Protein-peptide interactions are often associated with large-scale conformational changes that are difficult to study either by classical molecular modeling or by experiment. Recently, we have developed the CABS-dock method for flexible protein-peptide docking that enables large-scale rearrangements of the protein chain. In this study, we use CABS-dock to investigate the binding of the p53-MDM2 complex, an element of the cell cycle regulation system crucial for anti-cancer drug design. Experimental data suggest that p53-MDM2 binding is affected by significant rearrangements of a lid region - the N-terminal highly flexible MDM2 fragment; however, the details are not clear. The large size of the highly flexible MDM2 fragments makes p53-MDM2 intractable for exhaustive binding dynamics studies

SUBMITTER: Ciemny MP 

PROVIDER: S-EPMC5131342 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature