Quantum Chemical Study On Mechanism Of Ribosomal Peptide Bond Formation Catalyzed By Peptidyl Transferase

In this work, a series of theoretical methods were employed to investigate the reaction mechanisms of ribosomal peptide bond formation catalyzed by peptidyl transferase. The thesis consists of three chapters, including (1) basic theory and computational methods. (1) Theoretical study on mechanism of ribosomal peptide bond formation catalyzed by peptidyl transferase. (2) Theoretical study on mechanism of ribosomal peptide bond formation catalyzed by peptidyl transferase in mutation. (3) Quantum mechanical and molecular dynamics simulations calculations on other possible mechanisms of ribosomal peptide bond formation catalyzed by peptidyl transferase.In th first chapter, Ab initio methods , density functional theory and transition state theory were briefly introduced.For the studies described in the second chapter, reaction pathways and free energy barriers for the model reaction of the peptide bond synthesis were studied by performing Ab initio calculation. Two self-consistent reaction field(SCRF) methods were used to calculate of the whole reaction pathway. These results indicate that the free energy barry of the rate-determining step in our model is lower than the free energy barry of the rate-determining step in Merz's model, these show that the present theoretical reaction mechanism is a potential and competitive one for the reaction modeling of the ribosomal peptide synthesis.In the third chapter, first-principles electronic structure calculations were performer to study the reaction mechanisms of ribosomal peptide bond formation catalyzed by 9-methyl Guanine or 1-methyl Uracil instead of Adenine. These results indicate that substrate position is important.In the last chapter, molecular dynamics simulations and quantum mechanical were performed to study the other possible mechanism of ribosomal peptide bond formation catalyzed by peptidyl transferase. These results indicate our model is a potential and competitive one for reaction modeling for the ribosomal peptide synthesis.