Study On Structure And Function Of Two Kinds Of Important Proteines Based On Md Simulation

Molecular dynamics simulations are important tools for understanding the physical basis of the structure and function of biological macromolecules. MD simulations can provide the ultimate detail concerning individual particle motions as a function of time. Thus, they can be used to address specific questions about the properties of a model system, often more easily than experiments on the actual system.In this thesis, we use two examples to show the applications of MD simulations on biology investigations. One is simulating the T1lipase at different temperatures. T1lipase is a thermoalkalophilic enzyme derived from Geobacillus zalihae strain T1and it was with a perfect stability that is an important criterion for a sustainable industrial operation economically. So we want to find out why the T1lipase is so stable and high active at high temperature. By analysis, the structure of T1lipase at60℃and70℃is more stable, especially the distance between the two a helixes making up the active pocket could maintain in a specific range. This could keep water for the hydrolysis reaction near the active site for a long time. We also found that the hydrophobic interaction is main force to cause the different structural changes of T1lipase at diferernt temperature. Finally, another thermostable enzyme named L1lipase was simulated, and yielded a similar Conclusion with T1lipase. It is presumed that the same catalytic mechanism may exist widely in various thermostable enzymes.The other instance is the simulation of the fibroblast growth factor9(FGF9). Fibroblast growth factor9(FGF9) is one of the members of fibroblast growth factors'family. In the early stages of skeletal growth, the function of FGF9is to enlarge the area of the cartilage; In the later stages of skeletal growth, the major function of FGF9is to adjust vascularization for growth plate and osteogenetic process. Biochemical analysis reveals that the identified FGF9mutation (Ser99Asn) as a potential cause of multiple synostoses syndrome (SYNS). So we performed computational studies on wild-type and mutant FGF9separately. From the correlation of the3D structure of the wild-type and mutant FGF9, We found that the FGF9has a well-ordered C-terminal structure, which can reduce its homodimerization ability so as to break the monomer-dimer equilibrium in the FGF signaling, which is considered as a key factor to regulate extracellular matrix affinity and tissue diffusion in the FGF signaling pathway. FGF9WT monomer can preferentially form a homodimer owe to its comparatively lower binding free energy. In contrast, FGF9S99N monomer is preferred to bind with FGFR3c receptor to form an inactive complex, leading to impair FGF signaling. The impaired FGF signaling is believed to be a potential cause of human synostoses syndrome. So the result from the simulation successfully revealed the pathogenic mechanism on FGF9. To sum up the above arguments, these results available from this thesis make clear that the applications of molecular dynamics will play an even more important role for our understanding of biology in the future.