Study Of All-Atom Simplified Model And Statistical Analysis Of Equilibrium States

In molecular dynamic simulation,the common method using for studying the folding of protein,there are two aspects to consider:simulation resolution and calculation speed.About the simulation res-olution,models exists including all atom model and coarse-grained model.The all atom model considers the atomic interaction in protein for studying the connection between the structure and folding of protein and its atoms' location.On the other hand,coarse-grained model is used for studying how the interaction between residus influence by simplifying the residue to a bead.Restricted by computer performance,the simulation of all atom is much slower than coarse-grained model,which mean sometimes coarse-grained model is more suitable for reaching the time scale of biomolecular functional movement.In the selection of energy function,there are something to consider:close to real force and minimal frustration.Experi-enced force field is considered more close to real force and show the real action,but show rough energy profile which means long sampling time.On the other hand,Go model's smoother energy profile depen-dent on the topology structure show minimal frustration which can speed up the sampling of construction.The all atom Go model proposed in this thesis simplifies the all atom model and chooses the Go model for achieving the purpose of accelerating the sampling and guaranteeing certain resolution.By using the AA Go model,this thesis studied the kinetic and thermodynamic of WW Domain which found that more than one pathways for folding exsist such as,(i)?land ?2 fold first,then ?2and ?3 fold,(?)?2and ?33 fold first,then ?2and 133 unfold a little,then ?1,?2and ?3 fold at the same time.The thermodynamic analysis of WW Domain,show that the melting temperature and thermodynamic stability both meet the data from experiment.For studying the influnce of denaturant on the portein folding,the MTM theory was used to add the implicit solvent in.The result shows that as the concentration of denaturant rise up,the melting temperature drop down and the specific heat rise up,the rate of folding drop down and the rate of unfolding rise up and the kinetic show the chevron plots.Besides,the equilibrium states of the protein simulation trajectories were studied by using the AA Go model and the coarse-grained model according to the work of Xiaohu Hu.As the result of Hu's work,the normalized autocorrelation function drop down as lag time rise up,and the rate of drop down has linear correlation with the total observation time of the dynamical process.However,in this thesis,the result that as the total observation time rise up,the rate will come to a platform instead of rising up linearly.And,the location of this platform is unrelated with the temperature and folding.Overall,this thesis propose a all atom Go model which has studied the kinetic and thermodynamic of WW Domain,the influnce of denaturant and the statistical analysis of equilibrium states.