Quantum Mechanics And Molecular Mechanics To Study The Solvation Free Energy And The Catalytic Effect Of Enzymes

The solvation free energy plays an essential role in understanding the physicochemical properties in solution thermodynamics.To develop a set of accurate and effective theoretical methods to predict the solvation free energy has always been the focus of research.Born in 1920 developed the earliest polarized continuum model the Born solvation model,to calculate the solvation free energy for anions.But for polyatomic ion and the neutral molecule solvation free energy,due to the solvation radius was not well defined,would lead to the final result differed greatly from the experimental value.Therefore,to solve this problem,many researchers used different correction methods to correct the model,but these correction methods all have problems such as huge computation efforts and complex correction processes.A hybrid solvation model with the first solvation shell is proposed to calculate the solvation free energy.The hybrid solvation model combines the Born solvation model with quantum mechanics and molecular mechanics methods to calculate the solvation free energy.The potential energy curve in the gas phase is then combined with solvation free energy calculated in this way to predict the reaction curve in water.Finally,the experimental values of solvation free energy and energy barrier for 20 bimolecular nucleophilic substitution reactions are compared with our predicted values.The comparisons show that our prediction values are reliable.In addition to calculating the solvation free energy using quantum mechanics and molecular mechanics methods,we have also studied the catalytic effects of the S_N2reaction mechanism of haloalkane dehalogenase enzyme with substrate 1,2-dichloroethane.Enzymes play a fundamental role in many biological processes.By removing the three main active-site residues one by one from Haloalkane dehahogenase,we have found two catalytic descriptors:one descriptor is the distance difference between the breaking bond and the forming bond,and the other is the charge difference between the transition state and the reactant complex.Both descriptors scale linearly with the reaction energy barriers,with the three residue case having the smallest energy barrier and the zero residue case having the largest.These results demonstrate that,as the number of residues increases from zero to three,the synchronized bond breaking and formation process is speeded up,as well as the charge transfer process.In other words,the catalytic effects increase.The obtained two descriptors are used to predict the reactivity of this reaction in water.Both predicted barrier heights agree with the calculated one using a quantum mechanics and molecular dynamics approach,indicating that the water solvent hinders the reactivity.The barrier height predicted with the charge transfer descriptor also agrees well with the experimental result.This study shows that catalytic descriptors can be used to describe the performance of catalytic reactions with enzymes.In this paper,the first chapter mainly introduces the development of quantum chemistry and background of the research content involved in this paper;The second chapter introduces the theoretical methods used in our practical work,such as the derivation of Born solvation model,mixed quantum mechanics/molecular mechanics method,NEB method and SPC/E water molecular model;In the third chapter,we introduce the calculation process of the solvation free energy by using the hybrid solvation model with first solvation shell;In chapter 4,we mainly introduce the catalytic effect of haloalkane dehalogenase enzyme with 1,2-dichloroethane,and how to define the distance descriptor and charge descriptor;The fifth chapter is the summary and outlook.