Study On Protein Folding By Complex Network

The study of protein molecules is one of the kernel research fields in life science, which is also an important direction for biology to develop quantitative approaches in this later genetic age.Protein folding is the most important unrealized question in the molecule biology.The problem to be solved is how protein sequences determine their unique three-dimensional structure.Human genome project and subsequent proteotomic technology bring biology into system scientific era.Application of Complex network in organism becomes one branch of systems biology.Complex network theory abstracts the interactions among multi-individual into geometry structure by constructing network,and obtains more understanding from (about) realistic system by analyzing element and its distribution and clique characteristic.A protein molecule can be treated as a complex network with each residue simplified as a node and the interaction between them as a link.Recently, complex network immits bran-new ways and means to study protein folding and the relation between structure and function.In this thesis,we focus on identifying the key residues in protein folding and effect of network topology on protein folding kinetics.In Chapter One,the following three problems are discussed:â…°.the composing and structure of protein;â…±.the origin of protein folding,folding pathway,folding course and the thermodynamics hypothesis and dynamics hypothesis during folding;â…².application development of complex network in protein folding research.In Chapter Two,the complex network theory is introduced briefly.Firstly,some important static geometrical parameters are discussed,which include degree and its distribution,shortest path,clustering coefficient,etc.Then,several important network models are analysised,which contain regular network,random network,small-world network and scale-free network.In Chapter Three,the hydrophobic core residues and nucleus residues are identified by small-world network approach and molecule dynamics simulation.First, the amino acid networks are constructed based on a set of 91 proteins selected from the Protein Data Bank(PDB),including four structure types.It shows that the amino acid networks have typical small-world property by calculating network parameters. The native structures of GB1,LB1,SH3 are modeled as amino acid networks and the hydrophobic core residues are identified by the analysis of the betweenness.Then, two independent high temperature unfolding MD simulations for GB1 and CI2 are performed respectively.The amino acids are divided into two classes:hydrophobic residues and hydrophilic residues and the links between them are analyzed for three states.Last,the transition states are found by analyzing the conformational cluster of the structures on the unfolding trajectory,and the nucleus residues of GB1 and CI2 are identified by the analysis of the betweenness of transition states.In Chapter Four,the different influence of long-range and short-range interactions on topology and folding kinetics of two- and three-state proteins are focused on.The networks are constructed at three length scales:Protein Structure Networks(PSNs),Long-range Interaction networks(LINs) and Short-range Interaction networks(SINs).These networks are systematically analyzed to focus on their topology including clustering coefficients,shortest path length,average degree, degree distribution and assortative mixing behavior of the amino acid nodes.To uncover the relationship between structural properties and folding kinetics of the proteins,the correlations of protein network parameters with protein folding rate(lnk_f) and topology parameters contact order(CO) are analyzed.The different influence of long-range and short-range interactions on two- and three-state folding kinetics is found.In Chapter Five,the calculating process and its results are discussed and the main conclusions are given.