Protein folding by zipping and assembly. Export

@article{citeulike:1512300, abstract = {How do proteins fold so quickly? Some denatured proteins fold to their native structures in only microseconds, on average, implying that there is a folding "mechanism," i.e., a particular set of events by which the protein short-circuits a broader conformational search. Predicting protein structures using atomically detailed physical models is currently challenging. The most definitive proof of a putative folding mechanism would be whether it speeds up protein structure prediction in physical models. In the zipping and assembly (ZA) mechanism, local structuring happens first at independent sites along the chain, then those structures either grow (zip) or coalescence (assemble) with other structures. Here, we apply the ZA search mechanism to protein native structure prediction by using the AMBER96 force field with a generalized Born/surface area implicit solvent model and sampling by replica exchange molecular dynamics. Starting from open denatured conformations, our algorithm, called the ZA method, converges to an average of 2.2 A from the Protein Data Bank native structures of eight of nine proteins that we tested, which ranged from 25 to 73 aa in length. In addition, experimental Phi values, where available on these proteins, are consistent with the predicted routes. We conclude that ZA is a viable model for how proteins physically fold. The present work also shows that physics-based force fields are quite good and that physics-based protein structure prediction may be practical, at least for some small proteins.}, address = {*Department of Pharmaceutical Chemistry and Graduate Group in Biophysics, University of California, San Francisco, CA 94143.}, author = {Ozkan, S. B. and Wu, G. A. and Chodera, J. D. and Dill, K. A.}, citeulike-article-id = {1512300}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0703700104}, citeulike-linkout-1 = {http://www.pnas.org/content/104/29/11987.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/104/29/11987.full.pdf}, citeulike-linkout-3 = {http://www.pnas.org/cgi/content/abstract/104/29/11987}, citeulike-linkout-4 = {http://view.ncbi.nlm.nih.gov/pubmed/17620603}, citeulike-linkout-5 = {http://www.hubmed.org/display.cgi?uids=17620603}, day = {17}, doi = {10.1073/pnas.0703700104}, issn = {0027-8424}, journal = {Proc Natl Acad Sci U S A}, keywords = {gb, protein\_folding}, month = {July}, number = {29}, pages = {11987--11992}, posted-at = {2009-06-21 05:39:45}, priority = {2}, title = {Protein folding by zipping and assembly.}, url = {http://dx.doi.org/10.1073/pnas.0703700104}, volume = {104}, year = {2007} }

TY - JOUR ID - citeulike:1512300 L3 - citeulike-article-id:1512300 N2 - How do proteins fold so quickly? Some denatured proteins fold to their native structures in only microseconds, on average, implying that there is a folding "mechanism," i.e., a particular set of events by which the protein short-circuits a broader conformational search. Predicting protein structures using atomically detailed physical models is currently challenging. The most definitive proof of a putative folding mechanism would be whether it speeds up protein structure prediction in physical models. In the zipping and assembly (ZA) mechanism, local structuring happens first at independent sites along the chain, then those structures either grow (zip) or coalescence (assemble) with other structures. Here, we apply the ZA search mechanism to protein native structure prediction by using the AMBER96 force field with a generalized Born/surface area implicit solvent model and sampling by replica exchange molecular dynamics. Starting from open denatured conformations, our algorithm, called the ZA method, converges to an average of 2.2 A from the Protein Data Bank native structures of eight of nine proteins that we tested, which ranged from 25 to 73 aa in length. In addition, experimental Phi values, where available on these proteins, are consistent with the predicted routes. We conclude that ZA is a viable model for how proteins physically fold. The present work also shows that physics-based force fields are quite good and that physics-based protein structure prediction may be practical, at least for some small proteins. IS - 29 JF - Proc Natl Acad Sci U S A SN - 0027-8424 AD - *Department of Pharmaceutical Chemistry and Graduate Group in Biophysics, University of California, San Francisco, CA 94143. EP - 11992 TI - Protein folding by zipping and assembly. VL - 104 SP - 11987 KW - gb KW - protein_folding AU - Ozkan, SB AU - Wu, GA AU - Chodera, JD AU - Dill, KA PY - 2007/07/17/ UR - http://dx.doi.org/10.1073/pnas.0703700104 ER -