Study On The Binding Free Energy Of RS-RGD Based On ABEEM??-GB/SA Method

Many chemical reactions in human body will have important effects on human's own condition.It is very important to study the binding free energy between receptors and ligands in aqueous solution.In this thesis,a series of protein structures containing Arg-Gly-Asp(RGD)sequence are selected from Protein Data Bank.We combines the RGD fragments from PDB with the synthetic receptor RS as their RS-RGD complexes,which denote the experimental structures.Next,the thesis defines the other kind of RS-RGD,whose RGD is obtained from ABEEM?? force field simulation.And the later ones are called theoretical structures.The binding free energies of between RS and RGD of experimental and theoretical structures are calculated.The specific research contents are as follow:1.By using the ABEEM s p fluctuating charge model,the molecular dynamics simulation of RS receptor,RGD ligand and RS-RGD complex were conducted respectively at298.15 K and NVT ensemble.A water box with 25.0 ? × 25.0 ?× 25.0 ? is selected.The simulation time is 1 ns.RMSDs of non-hydrogen atomic coordinates and initial structure non-hydrogen atomic coordinates are calculated.We can find that whether the experimental structure or theoretical structure,whether RS receptor,RGD ligand or RS-RGD complex,their RMSDs tend to their respective stable values after 100 ps,which show that the system reaches dynamic equilibrium after 100 ps.2.Solvation free energies of RS receptor,RGD ligand and RS-RGD complex are calculated by the ABEEM??-GB/SA fluctuating charge force field.At the same time,the thesis calculates the detailed polar and nonpolar parts of the total solvation free energy.The polar part of the solvation free energy is calculated by the GB model,and the nonpolar part is calculated by the solvent accessible surface area(SASA)method.The results show that RGD and its complex are soluble.RGD and its complex can strongly interact with water.3.Similarly,the free energy and entropy contribution of receptor RS,ligand RGD and RS-RGD complex are calculated by ABEEM?? fluctuating charge force field.Based on the normal mode analysis,we calculated the vibrational entropy.4.Binding free energy of RS-RGD complex is the summation of the change of their total free energy,solvation free energy and entropy contribution of the system.The result obtained by ABEEM?? polarizable force field is close to the experimental value.It shows that our ABEEM?? fluctuating charge force field is a very good performance field model.The simulation structures built by ABEEM?? are reasonable,and the molecular properties calculated by ABEEM?? are accurate.