An in silico analysis of the binding modes and binding affinities of small molecule modulators of PDZ-peptide interactions.

ABSTRACT: Inhibitors of PDZ-peptide interactions have important implications in a variety of biological processes including treatment of cancer and Parkinson's disease. Even though experimental studies have reported characterization of peptidomimetic inhibitors of PDZ-peptide interactions, the binding modes for most of them have not been characterized by structural studies. In this study we have attempted to understand the structural basis of the small molecule-PDZ interactions by in silico analysis of the binding modes and binding affinities of a set of 38 small molecules with known K(i) or K(d) values for PDZ2 and PDZ3 domains of PSD-95 protein. These two PDZ domains show differential selectivity for these compounds despite having a high degree of sequence similarity and almost identical peptide b

SUBMITTER: Tiwari G 

PROVIDER: S-EPMC3738590 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature