Effects of Charge Interactions in Binding Processes

ITHURALDE, RE; BEST, R; TURJANSKI, AG

Workshop; Molecular-based Multiscale Modeling and Simulation Workshop; 2012

Pan American Science Institute

Charge interactions play major roles in the processes of folding and of binding of proteins. These roles have been extensively studied by means of experimental and computational methods for globular proteins. In particular, the influence of ionic force has been studied using Brownian Dynamics with several model systems. We intend to develop a flexible model capable of reproducing experimental data. We have previously studied the mechanism of folding and binding by means of computer simulations with a simple go-model like potential [2]. One key feature that is only indirectly included in such models is the role of charge interactions in protein-protein recognition. [1] Here we consider the role of charge interactions in the folding and binding process of an IUP and two structured proteins. We complement the original potential energy surface, represented by an amino-acid-type dependent (Miyazawa-Jernigan) attractive term for native contacts and a repulsive potential for non-native contacts with an explicit electrostatic interaction between charged groups. We consider the effect of these changes on the potential of mean force and the binding kinetics for the KIX-KID system. We consider the effect in kinetics of two different electrostatic potentials for the ubiquitin-Vps27 UIM system and another for the Barnase-Barstar system.