Molecular Dynamics Simulation Of Biomechanics Behavior Of Collagen Molecule In Osteogenesis Imperfecta

The macroscopic mechanical performance of human body highly depends on the mechanical performance response of biomaterials such as cells and proteins in micro/nano scale.Therefore,the study of the mechanical response of biomaterials constituting the human body and the impact of various physical and chemical microenvironments on mechanical behavior of biomaterials plays significant role in exploring the pathogenesis of some diseases.Osteogenesis imperfecta is a rare clinical disease.Its manifestation in animals and human body is a special manifestation of the mechanical property response of microscopic materials in organisms.At present,various imaging methods and gene testing have confirmed that the main cause of osteogenesis imperfecta is due to the gene mutation produced by type I collagen.Based on the pathogenesis of osteogenesis imperfecta,this dissertation characterized the mechanical properties of type I collagen under different mutations,and quantitatively analyzed the mechanical dynamic response of collagen,which is of great significance for understanding the biomechanical behavior of collagen and its pathological and physiological phenomena.The specific research contents are as follows:Firstly,based on the pathogenic mechanism of brittle bone disease in mice,two groups of heterotrimeric and homotrimeric collagen models were established.The tensile mechanical loading of the two groups of collagen was carried out under the simulated physiological microenvironment.The biomechanical mechanical responses of the two groups of collagen were compared and analyzed,and the heterotrimeric and homotrimeric collagen models were obtained from several analysis indexes such as internal bond action,solvent accessible surface area and radius of gyration The main reason for the difference of mechanical properties of homotrimer.Secondly,according to the pathogenesis of human osteogenesis imperfecta,an all atom molecular dynamics model of human type I collagen was established.Under the action of simulated physiological microenvironment,four groups of different point mutant collagen were loaded with tensile mechanics and three-point bending mechanics,and analyzed in depth under different mechanical property evaluation indexes,Finally,the effects of different degrees of mutation on the structural stability and mechanical properties of collagen were deeply analyzed.In summary,by studying two groups of models of heterotrimeric and homotrimeric collagen and different point mutant collagen,the pathological correlation between two similar diseases of mouse brittle bone disease and human osteogenesis imperfecta was analyzed,and the biomechanical mechanical response of collagen in osteogenesis imperfecta was simulated by molecular dynamics simulation.The bridge between osteogenesis imperfecta and collagen mutation in organism is constructed.