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Krantz","year":"2002","journal-title":"J Mol Biol"},{"key":"ref78","doi-asserted-by":"crossref","first-page":"11837","DOI":"10.1073\/pnas.0901178106","article-title":"Experimental determination of upper bound for transition path times in protein folding from single-molecule photon-by-photon trajectories","volume":"106","author":"HS Chung","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref79","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1016\/j.bpj.2011.09.013","article-title":"GB1 is not a two-state folder: Identification and characterization of an on-pathway intermediate","volume":"101","author":"A Morrone","year":"2011","journal-title":"Biophys J."},{"key":"ref80","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.bpj.2014.06.037","article-title":"Complex pathways in folding of protein G explored by simulation and experiment","volume":"107","author":"LJ Lapidus","year":"2014","journal-title":"Biophys J"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"17772","DOI":"10.1073\/pnas.1201794109","article-title":"Folding pathways of proteins with increasing degree of sequence identities but different structure and function","volume":"109","author":"R Giri","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref82","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1038\/nsb0994-584","article-title":"A short linear peptide that folds into a native stable beta-hairpin in aqueous solution","volume":"1","author":"FJ Blanco","year":"1994","journal-title":"Nat Struct Biol"},{"key":"ref83","doi-asserted-by":"crossref","first-page":"6004","DOI":"10.1021\/bi00185a041","article-title":"NMR solution structure of the isolated N-terminal fragment of protein-G B1 domain. Evidence of trifluoroethanol induced native-like beta-hairpin formation","volume":"33","author":"FJ Blanco","year":"1994","journal-title":"Biochemistry"},{"key":"ref84","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1002\/pro.5560031106","article-title":"Fast folding of a prototypic polypeptide: the immunoglobulin binding domain of streptococcal protein G","volume":"3","author":"J Kuszewski","year":"1994","journal-title":"Protein Sci"},{"key":"ref85","doi-asserted-by":"crossref","first-page":"7976","DOI":"10.1073\/pnas.0402684101","article-title":"Phi-value analysis and the nature of protein-folding transition states","volume":"101","author":"AR Fersht","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref86","doi-asserted-by":"crossref","first-page":"8004","DOI":"10.1073\/pnas.0708411105","article-title":"Simulation of Top7-CFr: A transient helix extension guides folding","volume":"105","author":"S Mohanty","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref87","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1002\/prot.24295","article-title":"Folding of Top7 in unbiased all-atom Monte Carlo simulations","volume":"81","author":"S Mohanty","year":"2013","journal-title":"Proteins"},{"key":"ref88","doi-asserted-by":"crossref","first-page":"5915","DOI":"10.1073\/pnas.1218321110","article-title":"Atomic-level description of ubiquitin folding","volume":"110","author":"S Piana","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref89","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1126\/science.1208351","article-title":"How Fast-Folding Proteins Fold","volume":"334","author":"K Lindorff-Larsen","year":"2011","journal-title":"Science"},{"key":"ref90","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.sbi.2010.10.006","article-title":"Taming the complexity of protein folding","volume":"21","author":"GR Bowman","year":"2011","journal-title":"Curr Opin Struct Biol"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"5113","DOI":"10.1021\/jp508971m","article-title":"Water dispersion interactions strongly influence simulated structural properties of disordered protein states","volume":"119","author":"S Piana","year":"2015","journal-title":"J Phys Chem B"},{"key":"ref92","doi-asserted-by":"crossref","first-page":"9438","DOI":"10.1073\/pnas.1200678109","article-title":"Templates are available to model nearly all complexes of structurally characterized proteins","volume":"109","author":"PJ Kundrotas","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref93","doi-asserted-by":"crossref","first-page":"15674","DOI":"10.1073\/pnas.1314045110","article-title":"Assessing the utility of coevolution-based residue-residue contact predictions in a sequence- and structure-rich era","volume":"110","author":"H Kamisetty","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref94","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1093\/protein\/gzp030","article-title":"Assessing computational methods for predicting protein stability upon mutation: good on average but not in the details","volume":"22","author":"V Potapov","year":"2009","journal-title":"Protein Eng Des Sel"},{"key":"ref95","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1021\/ct3000469","article-title":"Modeling structural flexibility of proteins with Go-models","volume":"8","author":"P Jiang","year":"2012","journal-title":"J Chem Theory Comput"},{"key":"ref96","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1063\/1.1699114","article-title":"Equation of state calculations by fast computing machines","volume":"21","author":"N Metropolis","year":"1953","journal-title":"J Chem Phys"},{"key":"ref97","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S0009-2614(99)01123-9","article-title":"Replica-exchange molecular dynamics method for protein folding","volume":"314","author":"Y Sugita","year":"1999","journal-title":"Chem Phys Lett"},{"key":"ref98","doi-asserted-by":"crossref","first-page":"8154","DOI":"10.1063\/1.1364637","article-title":"Monte Carlo update for chain molecules: Biased Gaussian steps in torsional space","volume":"114","author":"G Favrin","year":"2001","journal-title":"J Chem Phys"},{"key":"ref99","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1002\/jcc.540130812","article-title":"The weighted histogram analysis method for free-energy calculations on biomolecules. I. The method","volume":"13","author":"S Kumar","year":"1992","journal-title":"J Comput Chem"},{"key":"ref100","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1016\/j.bpj.2015.08.015","article-title":"MDTraj: A modern open library for the analysis of molecular dynamics trajectories","volume":"109","author":"RT McGibbon","year":"2015","journal-title":"Biophys J"},{"key":"ref101","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1107\/S0108767305015266","article-title":"Rapid calculation of RMSDs using a quaternion-based characteristic polynomial","volume":"61","author":"DL Theobald","year":"2005","journal-title":"Acta Crystallogr Sect A Found Crystallogr"},{"key":"ref102","unstructured":"MacQueen JB. Some Methods for classification and analysis of multivariate observations. Proc Symposium on Mathematical Statistics and Probability. The Regents of the University of California; 1967. pp. 281\u2013297."},{"key":"ref103","doi-asserted-by":"crossref","first-page":"9459","DOI":"10.1073\/pnas.96.17.9459","article-title":"Cation-pi interactions in structural biology","volume":"96","author":"JP Gallivan","year":"1999","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref104","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1002\/prot.20417","article-title":"Cation-pi interactions in protein-protein interfaces","volume":"59","author":"PB Crowley","year":"2005","journal-title":"Proteins"},{"key":"ref105","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1107\/S0021889896008631","article-title":"Verification of protein structures: Side-chain planarity","volume":"29","author":"RWW Hooft","year":"1996","journal-title":"J Appl Crystallogr"}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1004960","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,22]],"date-time":"2018-10-22T13:08:57Z","timestamp":1540213737000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1004960"}},"subtitle":[],"editor":[{"given":"Robert L","family":"Jernigan","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2016,6,2]]},"references-count":105,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2016,6,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1004960","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,2]]}}}