Folding Kinetics Of Two-state Proteins Based On Random Walk Model In Native Contacts Number Space

Protein folding is one of the important unsolved problems in molecular biology.It is also regard as one of the important problems of biophysics in 21st century.After the human genome project,the wide gap between a great deal of gene and protein sequences and a small quantity of protein structures has become the bottleneck which limits the research of proteomics.One of the aspects of protein folding is the folding mechanism which concerns with the question of how a protein reaches its native structure from its denatured state. Protein folding mechanism can also lead to the better algorithms for protein structure prediction.Recently,different models have been established to address the two-state protein folding phenomena,e.g.,framework model,hydrophobic collapse model, nuclear-condensation model and folding funnel model,etc.Although these simulation-and experiment-based microscopic theories of folding kinetics could capture some of the potentially relevant aspects of real proteins to some extent,they generally cannot be responsible for the vast range of folding rates observed in experiments.Moreover, these models cannot explain the quantitive relationships between protein folding rates and their topological parameters.Consider that the protein folding process is driven by two kinks of interactions: the "stochastic interactions" of solvent molecules and the interatomic "order interactions" in polypeptide,and they dominate the different phases of protein folding, a protein folding model based on random walk in its native contacts number space is suggested in this thesis.This model allows us to illustrate many essential aspects of small protein folding phenomenon,such as the two-state process,the unique native structure,a large number of conformations and the fast folding to the native state,etc. Especially,by using this folding model,one can derive the observed relationship between the folding rate constant and the number of native contacts.Finally,other factors,such as the chain length,the number of cysteines,and the ratio of hydrophobic amino acids in protein etc,have also be analyzed that how they affect the folding rates.