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Ouyang Projects
Predicting protein folding rates from amino acid sequences
Abstract
Protein folding speeds are known to vary over more than 8 orders of magnitude. Plaxco, Simons, and Baker first showed a correlation of folding speed with the topology of the native protein. That and subsequent studies showed that if the native structure of a protein is known, it's folding speed can be predicted reasonably well through a logarithmic 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 found, first, that in 80 proteins, the largest such database of proteins yet studied, N_alpha is an excellent predictor of folding speeds of both two-state fast-folders and more complex multi-state folders. It supports the view that folding occurs by a mechanism of zipping and assembly, where shorter loops are entropically faster to form than longer ones. Second, we show that folding rates can also be predicted from amino acid sequences directly, without the need to know the native topology.
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References
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