The Molecular Dynamics Simulation Study Of PYL1 And HPPD

Molecular simulation has a significant impact on the study of the allosteric mechanism of protein,protein ligand binding modes,which are difficult to study by experiment method.In this thesis we use molecular dynamics simulations to study:The ABA receptor PYL1's allosteric mechanism;Binding modes between PYL1 receptor and it's inhibitors;binding modes between HPPD and its representative triketones inhibitors.Crystal structure shows that the PYL1's apo form and complex form has an opened/closed conformation difference in the cavity,but the specific mechanism for switching between the two forms was not explicit.In this thesis,molecular dynamics simulations of the apo enzyme and complex with ABA of PYL1 receptor were performed 1 microsecond,according to the analysis of the two simulation trajectorys,we propose a allosteric mechanism of PYL1 receptor.Abscisic acid(ABA)is recognized as one of the five plant hormones,due to it's poor stability and high cost of synthesis,unlike other plant hormones,ABA have not used to agricultural production at present.However,ABA has important relationship with the crop's drought,cold,salt and other stress resistances,so it's very important to develop of new abscisic acid analogs which have structural stability and low cost of synthesis.In our research,computational simulation method such as molecular docking,molecular dynamics simulations were used to study the binding models between the ABA or ABA analogues and ABA receptor PYL1.The simulation trajectories are all stable and the binding models the simulation got are similar to the crystal structure's conformation,and the water bridge in the crystal structure can stay stable along with the simulation,which means our simulations are reasonable.Further more,we performed molecular dynamics simulations of seven(#32,#68,#71,#98,AM1,AM2,AM3)Pyrabactin analogues which have reported activity data,and we utilize MM/PBSA method to calculate the binding free energy,the results are consistent with the reported activity data,which have verify the reasonableness of the simulation model that we established.On this basis we designed three different types of Pyrabactin analogues and carried out molecular docking,molecular dynamics simulations,binding free energy calculations,the information of our simulation can help us to design new ABA analogues,provides an important guiding significance.In addition,we used molecular modeling methods to explore the interactions between the triketones inhibitors and HPPD,after molecular docking we performed molecular dynamics simulations,and the MM/PBSA method was used to calculate the binding free energy,we get a good matching between the calculated value of free energy and biological activity.The study of binding models of HPPD lay the foundation for the design of triketones HPPD inhibitors.