| Study on the relationship between structure and function of protein is the main research content ofproteomics. Protein is an important basis for the composition of life, and the spatial structure of protein isthe foundation of a specific biological function. Structure analysis of protein is not only to get a specificstructure, but more concerned about the fluctuation and movement of structure-the dynamic structure ofprotein. Protein-protein interaction is the foundation of all life activities and the necessary condition for themetabolic activity of cells. Study on the protein structure and protein-protein interaction not only helps toreveal the protein structure affect the stability of the protein function, but also plays a vital role inunderstanding the regulation of protein and the relationship between structure and function of cell.In this paper, molecular dynamics (MD) simulation and flow molecular dynamics simulation (FMD)method were performed to study the structure stability of human normal prion protein and R220K mutantprion protein, and the interaction between human insulin-like growth factor (IGFs) and its binding protein6(IGFBP6).In the first part of this study, structure stability and mechanical properties of the wild type and R220Kmutant human prion protein are studied by using MD and FMD simulation. Structure stability anddynamics properties of two protein systems in the process of equilibrium MD simulation and the fluiddisturbance FMD were compared. Three α-helices of the human prion protein formed relatively rigidbarrier by cross arrangement to maintain the stability of structure of proteins in the equilibrium state anddisturbance conditions. While the β-sheet in two simulations have shown a variety of forms of behaviours,such as: elongation, twisting and unfolding etc. Through the comparison of the stability of wild type andmutant protein is found that the mutation-related residue220enhanced stability of H3helix. The results ofthis study provide a theoretical basis for the molecular mechanism of human prion related diseases.In the second part of this study, kinetic characteristics of structure of human prion protein in the MDprocess, FMD process and refolding process were studied. We analyzed the unfolding pathway of proteinin the external disturbances, the refolding pathway of two fold structure in the natural state. Three α-helixhydrophobic core play an important role in the structural stability of proteins. In the unfolding process, the helix core can resist external disturbance. In the refolding process, the helix core played the role ofscaffolding, contribute to its surrounding structure folding back. β-sheets are very active in all the processof simulation. β-sheet appears in higher probability in the refolding process in completely unfolded system,which may be related to the prion protein misfolding. This study provides a new perspective forunderstanding the molecular mechanism of prion protein stability, introduces new structural features forunderstanding these diseases and the early molecular mechanism of transition process of PrPc to rich inβ-folding conformation.In the third part of this research, we studied the interaction between IGFs and IGFBP6. Based on theexperimental data, we constructed144composite systems of IGFBP6-IGFs (IGF1and IGF2), scaned thekey interactions, and drawed the key binding sites distribution map, also summarized and compared theproperty of the key binding site. And the interaction mechanism between two proteins are analyzed further,we discussed the influence of the interaction energy, combined with the driving force, the contact area oftwo proteins. The information obtained in the present study will has important significance forunderstanding the dynamic model of protein-protein interaction, drug design, the stability of the protein. |
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