{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:52:11Z","timestamp":1791244331485,"version":"4.1.0"},"reference-count":57,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,5,28]],"date-time":"2019-05-28T00:00:00Z","timestamp":1559001600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2019,5,28]],"date-time":"2019-05-28T00:00:00Z","timestamp":1559001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"publisher","award":["RGP\u2010150"],"award-info":[{"award-number":["RGP\u2010150"]}],"id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Glycoprotein Ib\u03b1 (GpIb\u03b1) binding ability of A1 domain of von Willebrand factor (vWF) facilitates platelet adhesion that plays a crucial role in maintaining hemostasis and thrombosis at the site of vascular damage. There are both \u201closs as well as gain of function\u201d mutations observed in this domain. Naturally occurring \u201cgain of function\u201d mutations leave self\u2010activating impacts on the A1 domain which turns the normal binding to characteristic constitutive binding with GPIb\u03b1. These \u201cgain of function\u201d mutations are associated with the von Willebrand disease type 2B. In recent years, studies focused on understanding the mechanism and conformational patterns attached to these phenomena have been conducted, but the conformational pathways leading to such binding patterns are poorly understood as of now. To obtain a microscopic picture of such events for the better understanding of pathways, we used molecular dynamics (MD) simulations along with principal component analysis and normal mode analysis to study the effects of Pro1266Leu (Pro503Leu in structural context) mutation on the structure and function of A1 domain of vWF. MD simulations have provided atomic\u2010level details of intermolecular motions as a function of time to understand the dynamic behavior of A1 domain of vWF. Comparative analysis of the trajectories obtained from MD simulations of both the wild type and Pro503Leu mutant suggesting appreciable conformational changes in the structure of mutant which might provide a basis for assuming the \u201cgain of function\u201d effects of these mutations on the A1 domain of vWF, resulting in the constitutive binding with GpIb\u03b1.<\/jats:p>","DOI":"10.1002\/jcb.29052","type":"journal-article","created":{"date-parts":[[2019,5,28]],"date-time":"2019-05-28T05:59:23Z","timestamp":1559023163000},"page":"17847-17857","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Effects of Pro1266Leu mutation on structure and function of glycoprotein Ib binding domain of von Willebrand factor"],"prefix":"10.1002","volume":"120","author":[{"given":"Ahmad Abu Turab","family":"Naqvi","sequence":"first","affiliation":[{"name":"Center for Interdisciplinary Research in Basic Science Jamia Millia Islamia  Jamia Nagar New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed F.","family":"Alajmi","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy College of Pharmacy King Saud University  Riyadh KSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tabish","family":"Rehman","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy College of Pharmacy King Saud University  Riyadh KSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afzal","family":"Hussain","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy College of Pharmacy King Saud University  Riyadh KSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3663-4940","authenticated-orcid":false,"given":"Imtaiyaz","family":"Hassan","sequence":"additional","affiliation":[{"name":"Center for Interdisciplinary Research in Basic Science Jamia Millia Islamia  Jamia Nagar New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,5,28]]},"reference":[{"key":"e_1_2_9_1_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001721-199104000-00017"},{"key":"e_1_2_9_1_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/MBC.0b013e32834cb35d"},{"key":"e_1_2_9_1_4_1","first-page":"161","article-title":"Platelet\u2010vessel wall interactions in thrombosis and restenosis role of von Willebrand factor","volume":"59","author":"Hoylaerts MF","year":"1997","journal-title":"Verh K Acad Geneeskd Belg"},{"key":"e_1_2_9_1_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02981974"},{"key":"e_1_2_9_1_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.17.10396"},{"key":"e_1_2_9_1_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.107355"},{"key":"e_1_2_9_1_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.511220"},{"key":"e_1_2_9_1_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2010.03.003"},{"key":"e_1_2_9_1_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.1.164"},{"key":"e_1_2_9_1_11_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH12-07-0475"},{"key":"e_1_2_9_1_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.15709"},{"key":"e_1_2_9_1_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.11.7539"},{"key":"e_1_2_9_1_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2014.07.026"},{"key":"e_1_2_9_1_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsb0902-646"},{"key":"e_1_2_9_1_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2018.1546621"},{"key":"e_1_2_9_1_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2015.1134346"},{"key":"e_1_2_9_1_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2016.1189359"},{"key":"e_1_2_9_1_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmgm.2015.10.009"},{"key":"e_1_2_9_1_20_1","doi-asserted-by":"publisher","DOI":"10.1139\/bcb-2015-0132"},{"key":"e_1_2_9_1_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2015.1046934"},{"key":"e_1_2_9_1_22_1","first-page":"1","article-title":"Structure prediction and functional analyses of a thermostable lipase obtained from Shewanella putrefaciens","volume":"35","author":"Khan FI","year":"2016","journal-title":"J Biomol Struct Dyn"},{"key":"e_1_2_9_1_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2016.1179596"},{"key":"e_1_2_9_1_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2019.1610500"},{"key":"e_1_2_9_1_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2019.04.135"},{"key":"e_1_2_9_1_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.28312"},{"key":"e_1_2_9_1_27_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6MB00182C"},{"key":"e_1_2_9_1_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-016-5329-y"},{"key":"e_1_2_9_1_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.26257"},{"key":"e_1_2_9_1_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.28387"},{"key":"e_1_2_9_1_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-13-173"},{"key":"e_1_2_9_1_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2015.09.062"},{"key":"e_1_2_9_1_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.genrep.2016.12.007"},{"key":"e_1_2_9_1_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-11-548"},{"key":"e_1_2_9_1_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_2_9_1_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.20810"},{"key":"e_1_2_9_1_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl190"},{"key":"e_1_2_9_1_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku411"},{"key":"e_1_2_9_1_39_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20121221"},{"key":"e_1_2_9_1_40_1","doi-asserted-by":"publisher","DOI":"10.1139\/bcb-2018-0007"},{"key":"e_1_2_9_1_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bti486"},{"key":"e_1_2_9_1_42_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2015.1100552"},{"key":"e_1_2_9_1_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2017.07.010"},{"key":"e_1_2_9_1_44_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2016.1150203"},{"key":"e_1_2_9_1_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20291"},{"key":"e_1_2_9_1_46_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja9621760"},{"key":"e_1_2_9_1_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-658-0_11"},{"key":"e_1_2_9_1_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btl461"},{"key":"e_1_2_9_1_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.340110305"},{"key":"e_1_2_9_1_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw315"},{"key":"e_1_2_9_1_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2011.01.002"},{"key":"e_1_2_9_1_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2015.06.019"},{"key":"e_1_2_9_1_53_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0033583508004654"},{"key":"e_1_2_9_1_54_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1994.1017"},{"key":"e_1_2_9_1_55_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr900095e"},{"key":"e_1_2_9_1_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2007.05.021"},{"key":"e_1_2_9_1_57_1","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.105.064485"},{"key":"e_1_2_9_1_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10822-016-9919-y"}],"container-title":["Journal of Cellular Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcb.29052","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.29052","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcb.29052","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.29052","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T08:45:18Z","timestamp":1786351518000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcb.29052"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,28]]},"references-count":57,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2019,10]]}},"alternative-id":["10.1002\/jcb.29052"],"URL":"https:\/\/doi.org\/10.1002\/jcb.29052","archive":["Portico"],"relation":{},"ISSN":["0730-2312","1097-4644"],"issn-type":[{"value":"0730-2312","type":"print"},{"value":"1097-4644","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,28]]},"assertion":[{"value":"2019-03-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-04-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-05-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}