Theoretical Studies On Properties And Structured Search Strategy On Oligopeptides

Oligopeptides are significant biomolecules either as the building blocks of proteins or as the individual molecules.Obviously,theoretical studies on the former have critically important significance for understanding the latter,and have been the focus of a large panel of the contemporary researches.The dissertation covers several representative areas in the theoretical research field on these systems,we not only devoted to the theoretical studies on the conformations and properties of representative peptide systems utilizing quantum chemical calculations,but also try to develop a much more effective way to search for those meaningful structures.This Ph.D dissertation focuses on theoretical studies on properties and structured search strategy on oligopeptides,a briefly introduction of each chapter is given as follows.In Chapter 1,we firstly introduced the basic theories and conceptions of several quantum chemical calculations including several ab initio methods,empirical approaches,DFT methods and basis sets.Then,the main software packages adopted in this dissertation are also refered in the end of the chapter.In Chapter 2,the main research contents,typical works and important issues in the experimental and theoretical research field on polypeptides are briefly introduced and summarized.This chapter provides the research background and direction of this dissertation,at the same time.In Chapter 3,a computational approach is proposed here to account for the effect of the non-equilibrium cooling on the experimental spectra.The low energy conformers of dipeptides YG,WG and GW are obtained through thorough conformational searches.The structural features and equilibrium distributions of conformations and the energy barriers for conformer conversions are then determined.Three classes of transition energy barriers,high,medium and low,are found for the conversions among conformers with distinctly different,similar and the same structural types,respectively.The final conformation populations are determined by assuming an initial temperature of about 450K and allowing for only the conformation conversion with a low energy barrier to occur during the rapid cooling process.The results provide a natural explanation for the numbers of observed experimentally conformations.The theoretical conformation assignments are also in good agreement with the experimental IR data.In Chapter 4,systemic structural searches are performed to explore the coordination spaces of representative alkali and alkaline earth with dipeptides alanine-alanine and phenylalanine-alanine.Some analyses of the qualities of several theories on the description of peptides-metal ions complexes are referred.Moreover,we further discussed the coordination effect attributing to the cationic size and charge.At last,binding energies of the metal ions are determined by high-level DFT calculations,and the relavant experimental issues of IR are explained in connection with the theoretical calculations.In Chapter 5,the discrete states for the residue backbone second structures are determined through a systematic analysis of the structural information in the low energy conformations of various oligopeptides.Based on the analyzation of their combination rules for adjacent residues,a path splicing method with the restrictive combination is then proposed to reduce the dimensionality of searchable PES for locating the low energy conformations of polypeptides.New method is proven to be not only very efficient,but also highly reliable by the verification of some tripeptides,tetrapeptides,and pentapeptides.At the same time,the reduced PES dimensionality can also be used to improve the computational efficiency of other stochastic search methods.In Chapter 6,a complete description of the important conformations of five representative tetrapeptides is made through thorough explorations of their PESs.Careful analysis of structural features have been performed,showing that the backbone of all the important tetrapeptide conformations can be classified with five characteristic H-bond configurations.Connections between the characteristic H-bond configurations of tetrapeptides and their constituting dipeptides are found.A rationalized method of finding all the important conformations of tetrapeptide by splicing the conformations of its constituting dipeptides is therefore developed.The splicing method is found to be both efficient and reliable by reproducing all the important conformations of the above five tetrapeptides.At the end of chapter,the successful predictions of abundant secondary structures such as strands,helices,and turns for pentaglycine suggests the feasibility for protein structure prediction with our method.Chapter 7 presents a brief summary of the work in this thesis.