Molecular Recognition of Intrinsically Disordered Proteins Studied by All-Atom Molecular Simulation

Abstract

Coupled folding and binding exhibited by intrinsically disordered proteins (IDPs) was reproduced computationally by an enhanced conformational sampling method, multicanonical molecular dynamics. We treat biomolecules with an all-atom model immersed in an explicit solvent. A free-energy landscape, which is a road map for the biomolecular conformational changes, has been computed for two IDP-partner systems (NRSF–mSin3 and pKID–KIX). Native and non-native complex clusters distributed in the landscape, and free-energy barriers separated those clusters. Analyses have suggested that various encounter complexes can reach the native complex via multiple pathways with overcoming the free-energy barriers.