Predicting protein folding rates from geometric contact and amino acid sequence.
Protein folding speeds are known to vary over more than eight orders of magnitude. Plaxco, Simons, and Baker (see References) first showed a correlation of folding speed with the topology of the native protein. That and subsequent studies showed, if the native structure of a protein is known, its folding speed can be predicted reasonably well through a correlation with the "localness" of the contacts in the protein. In the present work, we develop a related measure, the geometric contact number, N (alpha), which is the number of nonlocal contacts that are well-packed, by a Voronoi criterion. We find, first, that in 80 proteins, the largest such database of proteins yet studied, N (alpha) is a consistently excellent predictor of folding speeds of both two-state fast folders and more complex multistate folders. Second, we show that folding rates can also be predicted from amino acid sequences directly, without the need to know the native topology or other structural properties.
Ouyang
Zheng
Z
Department of Bioengineering, University of Illinois at Chicago, Chicago, Illinois 60607, USA.
Liang
Jie
J
D000595:Amino Acid Sequence; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*
D011506:Proteins