TY - JOUR
T1 - Theoretical perspectives on protein folding
AU - Thirumalai, D.
AU - O'Brien, Edward P.
AU - Morrison, Greg
AU - Hyeon, Changbong
PY - 2010/6/9
Y1 - 2010/6/9
N2 - Understanding how monomeric proteins fold under in vitro conditions is crucial to describing their functions in the cellular context. Significant advances in theory and experiments have resulted in a conceptual framework for describing the folding mechanisms of globular proteins. The sizes of proteins in the denatured and folded states, cooperativity of the folding transition, dispersions in the melting temperatures at the residue level, and timescales of folding are, to a large extent, determined by N, the number of residues. The intricate details of folding as a function of denaturant concentration can be predicted by using a novel coarse-grained molecular transfer model. By watching one molecule fold at a time, using single-molecule methods, investigators have established the validity of the theoretically anticipated heterogeneity in the folding routes and the N-dependent timescales for the three stages in the approach to the native state. Despite the successes of theory, of which only a few examples are documented here, we conclude that much remains to be done to solve the protein folding problem in the broadest sense.
AB - Understanding how monomeric proteins fold under in vitro conditions is crucial to describing their functions in the cellular context. Significant advances in theory and experiments have resulted in a conceptual framework for describing the folding mechanisms of globular proteins. The sizes of proteins in the denatured and folded states, cooperativity of the folding transition, dispersions in the melting temperatures at the residue level, and timescales of folding are, to a large extent, determined by N, the number of residues. The intricate details of folding as a function of denaturant concentration can be predicted by using a novel coarse-grained molecular transfer model. By watching one molecule fold at a time, using single-molecule methods, investigators have established the validity of the theoretically anticipated heterogeneity in the folding routes and the N-dependent timescales for the three stages in the approach to the native state. Despite the successes of theory, of which only a few examples are documented here, we conclude that much remains to be done to solve the protein folding problem in the broadest sense.
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U2 - 10.1146/annurev-biophys-051309-103835
DO - 10.1146/annurev-biophys-051309-103835
M3 - Review article
C2 - 20192765
AN - SCOPUS:77952931294
VL - 39
SP - 159
EP - 183
JO - Annual Review of Biophysics and Biomolecular Structure
JF - Annual Review of Biophysics and Biomolecular Structure
SN - 1936-122X
IS - 1
ER -