Hydrophobic Binding Hot Spots of Bcl-xL Protein-Protein Interfaces by Cosolvent Molecular Dynamics Simulation.

ABSTRACT: Identifying binding hot spots in protein-protein interfaces is important for understanding the binding specificity and for the design of nonpeptide, small molecule inhibitors. Molecular dynamics simulation in the isopropanol/water cosolvent environment and in water was employed to investigate Bcl-xL protein, which has a highly flexible, large, and primarily hydrophobic binding site. Simulations of either the apo- or holocrystal structures of the Bcl-xL in pure water fail to generate conformations found in the cocrystal structures of Bcl-xL in complex with its binding partners due to hydrophobic collapse. In contrast, simulations in cosolvent starting either from the apo- or holocrystal structure of the Bcl-xL yield binding-site conformations similar to that found in the cocrystal structure

SUBMITTER: Yang CY 

PROVIDER: S-EPMC4018050 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature