{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T01:34:27Z","timestamp":1789781667939,"version":"4.0.1"},"reference-count":38,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2009,1,1]],"date-time":"2009-01-01T00:00:00Z","timestamp":1230768000000},"content-version":"vor","delay-in-days":853,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2006,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Collagen has a unique folding mechanism that begins with the formation of a triple\u2010helical structure near its C terminus followed by propagation of this structure to the N terminus. To elucidate factors that affect the folding of collagen, we explored the folding pathway of collagen\u2010like model peptides using detailed molecular simulations with explicit solvent. Using biased molecular dynamics we examined the latter stages of folding of a peptide model of native collagen, (Pro\u2010Hyp\u2010Gly)<jats:sub>10<\/jats:sub>, and a peptide that models a Gly \u2192 Ser mutation found in several forms of osteogenesis imperfecta, (Pro\u2010Hyp\u2010Gly)<jats:sub>3<\/jats:sub>\u2010Pro\u2010Hyp\u2010Ser\u2010(Pro\u2010Hyp\u2010Gly)<jats:sub>6<\/jats:sub>. Starting from an unfolded state that contains a C\u2010terminal nucleated trimer, (Pro\u2010Hyp\u2010Gly)<jats:sub>10<\/jats:sub> folds to a structure where two of the three chains associate through water\u2010mediated hydrogen bonds and the third is relatively separated from this dimer. Calculated free\u2010energy profiles for folding from this intermediate to the final triple\u2010helical structure suggest that further folding occurs at a rate of approximately one Pro\u2010Hyp\u2010Gly triplet per msec. In contrast, after 6 nsec of biased dynamics, the region N\u2010terminal to the Ser residue in (Pro\u2010Hyp\u2010Gly)<jats:sub>3<\/jats:sub>\u2010Pro\u2010Hyp\u2010Ser\u2010(Pro\u2010Hyp\u2010Gly)<jats:sub>6<\/jats:sub> folds to a structure where the three chains form close contacts near the N terminus, away from the mutation site. Further folding to an ideal triple\u2010helical structure at the site of the mutation is unfavorable as the free energy of a triple\u2010helical conformation at this position is more than 20 kcal\/mol higher than that of a structure with unassociated chains. These data provide insights into the folding pathway of native collagen and the events underlying the formation of misfolded structures.<\/jats:p>","DOI":"10.1110\/ps.062124606","type":"journal-article","created":{"date-parts":[[2006,8,30]],"date-time":"2006-08-30T22:12:48Z","timestamp":1156975968000},"page":"2166-2177","source":"Crossref","is-referenced-by-count":35,"title":["The folding mechanism of collagen\u2010like model peptides explored through detailed molecular simulations"],"prefix":"10.1002","volume":"15","author":[{"given":"Collin M.","family":"Stultz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0505141102"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2880131"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.070050097"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7695699"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.448118"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.235"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2002.5439"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-3233(05)70009-7"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(89)90093-4"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.540040211"},{"key":"e_1_2_5_12_1","doi-asserted-by":"crossref","DOI":"10.1002\/9780470141205","volume-title":"Advances in chemical physics","author":"Brooks C.L.","year":"1988"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2000.0761"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi992584r"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M407061200"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C200698200"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/bip.360330803"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0263-7855(96)00018-5"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemphys.2004.05.010"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.10321"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0134(19990501)35:2<133::AID-PROT1>3.0.CO;2-N"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(83)80306-4"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0408749102"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.478259"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp003020w"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.10344"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1999.2670"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.5103"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2005.04898.x"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp9839044"},{"key":"e_1_2_5_31_1","first-page":"2324","volume-title":"Harrison's principles of internal medicine","author":"Prockop D.L.","year":"2004"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16051-0"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.20478"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9991(77)90098-5"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444905024030"},{"key":"e_1_2_5_36_1","volume-title":"Chemical kinetics and dynamics","author":"Steinfeld J.I.","year":"1988"},{"key":"e_1_2_5_37_1","volume-title":"Biochemistry","author":"Stryer L.","year":"1988"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(02)00421-7"},{"key":"e_1_2_5_39_1","first-page":"13995","article-title":"Mutations that substitute serine for glycine \u03b1l\u2013598 and glycine \u03b1l\u2013631 in type I procollagen","volume":"265","author":"Westerhausen A.","year":"1990","journal-title":"J. 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