Abstract
Folding proteins into their native states requires the formation of
both secondary and tertiary structures. Many questions remain, however,
as to whether these form into a precise order, and various pictures
have been proposed that place the emphasis on the first or the second
level of structure in describing folding. One of the favorite test
models for studying this question is the B domain of protein A, which
has been characterized by numerous experiments and simulations. Using
the activation-relaxation technique coupled with a generic energy model
(optimized potential for efficient peptide structure prediction), we
generate more than 50 folding trajectories for this 60-residue protein.
While the folding pathways to the native state are fully consistent
with the funnel-like description of the free energy landscape, we find
a wide range of mechanisms in which secondary and tertiary structures
form in various orders. Our nonbiased simulations also reveal the
presence of a significant number of non-native beta and alpha
conformations both on and off pathway, including the visit, for a
non-negligible fraction of trajectories, of fully ordered structures
resembling the native state of nonhomologous proteins. (C) 2008
American Institute of Physics.
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