The Influence Of Codon Usage Bias And RNA Structure On Protein Folding Rate

Protein is one of the most important biological macromolecules,involved in almost all kind of life activities. It usually could be folded from unfolding state to native conformation with three-dimensional structure rapidly and reliably. Since the function of protein is determined by its structure, Misfolded proteins may produces inactive proteins, cause cell death or tissue damage and be implicated in prion diseases,such as Alzheimer’s,Parkinson’s and CJD. All prion diseases are currently untreatable and always fatal. Protein folding is the most fundamental and important process for all biological systems. It is a complicated and a difficult theoretical problem as well as one of the core issue of molecular biology, but it is now still one of the most puzzling and as yet unresolved question to us.The main research contents are as follows:1. Based on the present small data of protein folding rates and related works, a bigger protein folding rates data were constructed, and the information of mRNA of each protein was added in the new data. For each protein, the codon usage bias of its corresponding mRNA sequence was calculated, then, for each kind of proteins, the correlation between protein coding rates and the codon usage bias of they corresponding mRNA sequence were analyzed. The results show that, for some codons, protein coding rates significantly correlate with the codon usage bias of their corresponding mRNA sequence. It means that synonymous codon usage bias may play animportant role in protein folding.2. In the earlier work, a bigger data of protein folding rates was constructed, in which the information of mRNA of each protein was added.On this bases, for each protein, the content of stem structure, the content of loop structure, the folding free energy and the flexibility of mRNA were calculated, then, the relationship between the folding rates and the mRNA secondary structure were analyzed. It is found that the folding rates show negative correlation with the contents of stem structure, and positive correlation with the content of loop structure, at the same time, it is found that the folding rates show positive correlation with the flexibility of mRNA.While the proteins were divided into different groups according to their secondary structure and their folding types, further analysis show that, for each kind of protein, the flexibility of mRNA all is an influential factor for protein folding, but the contents of stem structure and the content of loop structure mainly influence on the folding rates of two-state proteins. The results indicated that the mRNA secondary structure play an important role in protein folding.3. Currently, the proteins are derived from different species in the study about the influence of synonymous codon usage bias on protein folding rate.In this article, considering the species differences of synonymous codon bias,the nucleoproteins of bacillus subtillis was selected as the samples. First, each of the nucleoprotein was cut into α-helices, β-strands and mixed-classsegments according to their secondary structure. Then, the information of its corresponding mRNA sequence of each peptide segment was found, the synonymous codon usage bias and the protein folding rate of corresponding peptide segments were calculated. On this basis, the correlation between synonymous codon usage bias and the corresponding peptide folding rate of bacillus subtillis were analyzed. It was found that some of codon usage bias were significantly correlated with the protein folding rate of the peptide segments for different secondary structures. Further analysis found, most of codons significant correlation with peptide folding rate are the high RSCU value of bacillus subtillis complete sequence and ribosomal sequence. The results show that the synonymous codon usage bias of bacillus subtillis plays an important role in protein folding.