Diversity in free energy landscape and folding pathway of proteins with the same native topology

Abstract

To elucidate the role of relative stability of subdomains in folding processes of multi-domain proteins, we have studied a free-energy landscape of c-type lysozyme by Monte Carlo simulations using a realistic lattice model with a Gō-like interaction. By varying the relative interaction strength of two subdomains as a parameter, we obtained a variety of the free-energy landscapes. Experimentally-observed diversity in folding processes of c-type lysozymes can then be described by this Gō-like model with only one variable parameter. The result demonstrates that folding of multi-domain proteins can be understood in the framework of the energy landscape theory.