Interdomain Allostery and Electrostatic Effects in Heat Shock Protein 70

I. J. GENERAL; I. BAHAR

Newport

Conferencia; Gordon Research Conference - Biopolymers; 2012

The versatile functions of the Heat Shock Protein 70 (Hsp70), such as chaperoning protein folding and regulating the intracellular trafficking, rely on the allosteric interactions between its two domains: the ATPase or nucleotide binding domain, NBD, and the substrate binding domain, SBD. Understanding the interdomain allostery of Hsp70 is key to the rational design of its inhibitors, yet the mechanism of allostery still remains a challenging problem. Here we apply a series of methods to understand these mechanisms, including sequence analysis, Gaussian network modeling and covariance matrix analysis. Additionally, we perform all-atom molecular simulations in order to establish the role of the highly charged ATP in interdomain communication.