The Structural Modeling And Dynamics Simulation Of EF-hand Domain In Parvalbumin

Protein structure determines the function of the protein.Protein function is closely related to its physiological characteristics.And just knowing the gene sequence does not allow us to fully understand the function of the protein.Since protein misfolding can lead to disease,the simulation of protein folding and structure helps to study the pathogenesis of many diseases.There are many different ways to study the problem of protein folding.The main experimental methods are X-ray crystal diffraction,Nuclear Magnetic Resonance(NMR)and cryoelectron.The theoretical methods mainly use molecular dynamics simulation.Molecular dynamics(MD)is often used to refine the three-dimensional structures of proteins and other macromolecules based on X-ray crystallography or NMR experiments.The computational efficiency is high and the properties of the entire molecule can be studied.The coarse-grained model will be used in the folding process and the folding of the macromolecular system for a long time,which can increase the simulation speed and reduce the computational complexity.The problem of protein folding is listed as an important topic of“biophysics in the 21st century”and it is of great significance to study it.In this thesis,we use the theory of topological soliton to model the domain of a typical EF-hand protein---parvalbumin.Glauber's kinetic Monte Carlo simulation algorithm was used to simulate the unbalanced unfolding-folding process of parvalbumin.By comparing the fitting structure with the experimental structure,the kinetic characteristics of the parvalbumin under the condition of temperature heat disturbance were revealed.The main work is as follows:(1)We mainly modeled the Asp8-Lys64 fragment of the experimental structure of parvalbumin(2PVB).Based on the theory of topological soliton,We perform the Z₂specification transformation on the experimental structure of the parvalbumin and analyze its eight-soliton structure.We use the Propro UI program to fit eight solitons,and finally get the parameters of the energy function of eight solitons and the minimum RMSD optimal configuration.From the parameters,we can know that protein torsion?is better than bond angle?in flexibility.By comparing the fitting structure with the experimental structure,we can find that the distribution of bond angle?and torsional angle?are very close.(2)Based on the Glauber algorithm,We use the method of Monte Carlo(MC)cooling with increasing temperature to simulate the non-equilibrium process of unfolding and refolding.We take the soliton solution of the energy function described by the parameter values as the initial conformation of each cycle and try different temperatures to study the influence of thermal disturbance on the clusters distribution of the final conformations.In general,the structure is stable at low temperatures.The simulation results were analyzed by parameters such as root mean square deviation(RMSD)and gyration radius(Rg).It can be found that the first EF-hand structure of the parvalbumin under thermal perturbation is relatively stable,whereas the second EF-hand structure with calcium ion binding is variable.In this paper,by the two processes of constructing a high-precision multi-soliton configuration and non-equilibrium kinetic simulation of the parvalbumin's domain,we finally analyzed the correlation between the conformational changes of parvalbumin and Ca²⁺binding.