Change in allosteric network affects binding affinities of PDZ domains: analysis through perturbation response scanning.

ABSTRACT: The allosteric mechanism plays a key role in cellular functions of several PDZ domain proteins (PDZs) and is directly linked to pharmaceutical applications; however, it is a challenge to elaborate the nature and extent of these allosteric interactions. One solution to this problem is to explore the dynamics of PDZs, which may provide insights about how intramolecular communication occurs within a single domain. Here, we develop an advancement of perturbation response scanning (PRS) that couples elastic network models with linear response theory (LRT) to predict key residues in allosteric transitions of the two most studied PDZs (PSD-95 PDZ3 domain and hPTP1E PDZ2 domain). With PRS, we first identify the residues that give the highest mean square fluctuation response upon perturbing the bin

SUBMITTER: Gerek ZN 

PROVIDER: S-EPMC3188487 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature