Steered Molecular Dynamics Simulation On The Structure Of Human Cystatin C Dimer

Human cystatin C (HCC) is a kind of Non-glycosylated protein, which is composed of 120 amino acids. It belongs to the cystatin type II super family members and widely exist in the human body. Research showed that the L68Q HCC mutant can form amyloid fiber depositions and cause disease in the human body. The formation of the aggregate is mainly relied on the domain swapping mechanism. In natural crystal state, only the dimer structure can be detected through the X-ray and NMR methods, but it’s difficult to get the wild type monomer structure. As a result, it could be the HCC dimer structure existence stability in the nature state. At present, the stably exist research of HCC was mainly focused on the monomer structure, the HCC dimer is rarely studied. In this paper, we adopt the steered dynamic simulation method to study the HCC dimer structure.Through the experiment, we drawn the following conclusion: the stability of HCC dimer is mainly maintained by the intermolecular interactions. These interactions are mainly distributed in two domain regions: AS and Helix-β2 region,β2 andβ3 region. Two residues on the AS region, Lys75 and Arge93, played the most important roles in the interactions. They are mainly through the strong hydrogen bonds and salt bridges to stabilize the two parts in dimer respectively. And there are three resides in theβ2 andβ3 region, Gln48, Asp65, Glu67, played the key roles in the interactions. They are connected mainly by hydrogen bonds, salt bridges and van der waals interactions to stabilize the two parts of the dimer in different periods of steered molecular dynamic process respectively. Our study has provided lots of new informations to study of systematic HCC mutations, and make the important contributions to the research of domain swpping mechanism research.