Performance Analysis On Molecular Mechanics Force Fields And Quantum Mechanics For Amino Acids And Small Peptides

Amino acids and peptides are significant biomolecules either as the building blocks of proteins or as the individual molecules.Theoretical studies on the amino acids and peptides have critically important significance both in theories and practices,and have been the focus of a large panel of the contemporary researches.This dissertation is devoted to the theoretical studies on the conformations and properties of representative amino acid and peptide systems utilizing quantum chemical calculations and molecular mechanics.The dissertation covers several representative areas and focal issues in the theoretical research field on these systems.The first chapter,There is a growing interest in the study of structures and properties of biomolecules in gas phase.Applications of force fields are highly desirable for the computational efficiency of the gas phase study.To help the selection of force fields,the performances of five representative force fields for gaseous neutral,protonated,deprotonated and capped amino acids are systematically examined and compared.The tested properties include relative conformational energies,energy differences between cis and trans structures,the number and strength of predicted hydrogen bonds,and the quality of the optimized structures.The results of BHandHLYP/6-311++G(d,p)are used as the references.GROMOS53A6 and ENCADS are found to perform poorly for gaseous biomolecules,while the performance of AMBER99SB,CHARMM27 and OPLSAA/L are comparable when applicable.Considering the general availability of the force field parameters,CHARMM27 is most recommended,followed by OPLSAA/L,for the study of biomolecules in gas phase.The second chapter,this chapter introduces theories of unfolded polypeptides and proteins,which provide background and guidance for our research work.The third chapter,we use ab initio methods to study the structure and character of amino acids,protonated,deprotonated amino acids and capped-amino acids.Global searching method was used here looking for the most stable structures.The same configurations were also optimized by five different force fields.Comparing the results of different force fields with the results of quantum mechanics,we can find the advantages and disadvantages of force fields for describing amino acids with different terminus.The fourth chapter,we studied the n-?*interactions for some dipeptides and tripeptides.The most stable conforms for dipeptides and tripeptides were calculated with ab initio method.Then we classified the structures into different basins with ?and ?.We found that many a,aL,PII configurations have n-?*interactions,which is consistent with other researchers' findings.The same proceedings were performed under different force fields,but with apparent differently results.We concluded that it is necessary to add an n-?*interaction function to improve the force fields.Chapter ?,we used molecular dynamics to simulate hydrogen bonds of capped-gfg and water in aqueous under AMBER force field.Instead of complex hydrogen-bond-network,simple hydrogen-bond-chain with water would complete various structures due to the hydrophobic effect.Chapter ?,a new "divide and conquer" method based on the discrete DA states and their combinations is developed to reduce the dimensionality of PES necessary for locating the low energy conformations of peptides.The new method is proven to be not only very efficient,but also highly reliable by providing the best results for the low energy conformations of representative tripeptides,tetrapeptides,and pentapeptides.The reduced PES dimensionality by the new "divide and conquer"approach can be used to improve the computational efficiency of a variety of conformational search methods,including both the systematic and stochastic search.Chapter ? presents a brief summary of the research results in this dissertation.