The Theory And Computational Simulation Of The Reaction Mechanism Of ATP Hydrolysis

Adenosine triphosphate (ATP) is the most direct source of energy in organisms. ATP provides a way to convert energy from ATP hydrolysis to biochemical processes, as a basic energy carrier in cellular metabolism. Understanding the ATP hydrolysis reaction is important in life sciences. In recent years, studies of the reaction mechanism of ATP hydrolysis in aqueous solution have made significant progress. However, the elucidation of the reaction mechanism is still under debate due to the limitations of calculation methods. In the present study, both the MEP reaction path and free energy profile were calculated. The main results of the dissertation are presented as follows:In chapter1, the theoretical methods used in this paper are introduced. These approaches include Hartree-Fock (HF) theory, density functional theory (DFT), and QMMM method.In chapter2, the computing methods, such as free energy calculation method, and NEB(Nudged Elastic Band) method used in this paper are described.In chapter3, the reaction mechanism of ATP hydrolysis in aqueous solution was studied and the reaction free energy profile was computed. ATP consists of three phosphate groups (triphosphate) and adenosine-composed of a ribose sugar and an adenine ring. The phosphoryl groups which start with the group closest to the ribose are referred to the alpha (α), beta (β), and gamma (γ) phosphates. The terminal y phosphate group of ATP is first hydrolyzed when energy is needed to drive anabolic reactions. According to the past research, the nucleoside fragment has little impact on this hydrolysis reaction. So, we divide ATP into two parts, the three phosphate groups are treated as the QM part and the rest of ATP as the MM part. The minimum energy path is searched using the nudged elastic band (NEB) method to connect the structures of the reactant and the product with a reaction path. This method is quite different from the past research, which predefined the reaction coordinates based on the reaction mechanism, either dissociative reaction or associative reaction. Instead, in this research, the reaction mechanism is determined after the MEP and the free energy are obtained.In chapter4, the summary and the perspective are given.