Theoretical Studies On The Structure And Properties Of CH₃COAla-Pro-TyrNHCH₃ Tetrapeptides In Aqueous Solution

It is an important topic of the studies on the conformations of polypeptides and their structures and properties in aqueous solutions.Firstly,based on the stable conformations of the dipeptides and tetrapeptides,the theoretical simulation initial structures of a series of CH3COAla-Pro-TyrNHCH3(APY)tetrapeptides were constructed and obtained by using ABEEMσπ polarizable force field.At the same time,the protein fragments containing xaa-Ala-Pro-Tyr-xaa extracted from PDB and Coil Library are their initial experimental structures.The structures and properties of the aqueous solution of APY tetrapeptides described above were studied by using the molecular simulation.The detailed research contents as follows.1.The stable conformations of the alanine,proline and tyrosine dipeptide molecules were used to construct the initial conformations of CH3COAla-PrNHCH3(AP)and CH3COPro-TyrNHCH3(PY)tripeptides.ABEEM polarizable force field and ab initio method were employed to optimize and obtain the stable conformations of tripeptide.Then the stable conformations mentioned above were used to construct the initial conformations of APY tetrapeptides.2.By using the ABEEMσπ fpolarizable force field,the molecular dynamics simulation of the APY tetrapeptides were carried out respectively at 298.15 K and NVT ensemble.A water box with 25.0 A × 25.0 A × 25.0 A was selected.The simulation time is 1 ns.RMSDs of non-hydrogen atomic coordinates of those molecules are calculated,compared with the stable.It can be found that whether the experimental structures or theoretical structures,their RMSDs tend to stable values after 100 ps,which show that these systems reach dynamic equilibrium after 100 ps.3.Free energies of APY tetrapeptides in aqueous solution are calculated in the terms of the ABEEM σπ polarizable force field in combination with the GB/S A model.At the same time,the thesis calculates the detailed polar and nonpolar parts of the total free energyies of solvation.The polar part of the free energy of solvation is calculated by the GB model,and the nonpolar part is calculated by the solvent accessible surface area(SASA)method.The results show that APY tetrapeptides are soluble.4.At the same time,different models including Hct,Still,Hct,Hct Still,Gk,Gk radius and Still corresponding to different force fields containing CHARMM,OPLS-AA,AMOEBA and AMBER in the Tinker package are used to calculate the free energies of solvation of the APY tetrapeptides.Compared with the results of the other models mentioned above,the results obtained by the ABEEM-GB/S A method are closer to those of ab initio method.It can be found that ABEEMσπ polarizable force field is a very good performance field model.The simulation structures constructed by ABEEM σπ polarizable force field are reasonable,and the molecular properties calculated by ABEEMσπ are accurate.