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

摘要

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), Ion-g-range order (LRO), total contact distance (TCD), chain topology parameter (CTP), and effective length (L-eff) 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 lnk(f) and nOCD with n=1.2, alpha=0.6 is found for two-state folders (correlation coefficient is -0.809, P-value<0.0001) and n=2.8, alpha=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, alpha=0.6 (correlation coefficient is 0.0943, P-value=0.661) and for two-state folders with n=2.8, alpha=1.5 (correlation coefficient is -0.235, P-value=0.2116). We also find that the average number of contacts per residue P-m in the interval of m for two-state folders is smaller than that for three-state folders. The probability distribution P(gamma) of residue having gamma pairs of contacts fits a Gaussian distribution for both two- and three-state folders. We observe that the correlations between square radius of gyration S-2 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. (C) 2004 Elsevier B.V. All rights reserved.