Investigating Characteristics of Folding Cores from Analyses of Folding Mechaniams on Multi-Transition Proteins by Means of a Coarse-Grained Go Model

Abstract

Though it has become clear that small and fast folding proteins have funnel shaped energy landscape, we have not know explicitly what and when happens in folding process. The knowledge of precise picture in each transition in the folding process of multi state proteins should provide the hints to elucidate the detailed folding processes.However, many hypotheses that try to explain the mechanisms of multi-state folding have been proposed (such as hypotheses regarding the packing of side chains after searching the protein's topology, those regarding a number of subdomains that form a distinct barrier, those regarding discrete two-dimensional and three-dimensional structure formation, and others) and we have not yet gained a precise understanding.To understand the mechanisms of multi-state folding, thermodynamic contributions of each component of the system, such as a main-chain, a side-chain and water, should be specified. It can be accomplished by comparing the simulation results of some models which has different resolution such as Ca-Go model, full-atom Go model and all-atom with explicit water.In the precedent study, as a first step, we showed that the difference in the shape of the free energy profiles could be interpreted by the number of the regions that folds cooperatively and degree of coupling of the regions by means of modified Ca-Go model.In this study, we apply the same method with previous work to other proteins which are suggested to fold into the native structures through multiple transitions and affirm the number of the barrier and stability of the intermediate states. We also investigate that the characteristics of the regions to contribute to barrier constructions.