Folding rate prediction using n-order contact distance for proteins with two- and three-state folding kinetics Original Research Article

It is a challenging task to understand the relationship between sequences and folding rates of proteins. Previous studies are found that one of contact order (CO), long-range order (LRO), total contact distance (TCD), chain topology parameter (CTP), and effective length (Leff) has a significant correlation with folding rate of proteins. In this paper, we introduce a new parameter called n-order contact distance (nOCD) and use it to predict folding rate of proteins with two- and three-state folding kinetics. A good linear correlation between the folding rate logarithm lnkf and nOCD with n=1.2, α=0.6 is found for two-state folders (correlation coefficient is −0.809, P-value<0.0001) and n=2.8, α=1.5 for three-state folders (correlation coefficient is −0.816, P-value<0.0001). However, this correlation is completely absent for three-state folders with n=1.2, α=0.6 (correlation coefficient is 0.0943, P-value=0.661) and for two-state folders with n=2.8, α=1.5 (correlation coefficient is −0.235, P-value=0.2116). We also find that the average number of contacts per residue Pm in the interval of m for two-state folders is smaller than that for three-state folders. The probability distribution P(γ) of residue having γ pairs of contacts fits a Gaussian distribution for both two- and three-state folders. We observe that the correlations between square radius of gyration S2 and number of residues for two- and three-state folders are both good, and the correlation coefficient is 0.908 and 0.901, and the slope of the fitting line is 1.202 and 0.795, respectively. Maybe three-state folders are more compact than two-state folders. Comparisons with nTCD and nCTP are also made, and it is found that nOCD is the best one in folding rate prediction.