{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T18:04:23Z","timestamp":1772129063931,"version":"3.50.1"},"reference-count":47,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,4,3]],"date-time":"2014-04-03T00:00:00Z","timestamp":1396483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["GM094623"],"award-info":[{"award-number":["GM094623"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["GM50789"],"award-info":[{"award-number":["GM50789"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Office of Science of the U.S. Department of Energy","award":["DE-AC02-05CH11231"],"award-info":[{"award-number":["DE-AC02-05CH11231"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Integrative structural biology attempts to model the structures of protein complexes that are challenging or intractable by classical structural methods (due to size, dynamics, or heterogeneity) by combining computational structural modeling with data from experimental methods. One such experimental method is chemical crosslinking mass spectrometry (XL\u2010MS), in which protein complexes are crosslinked and characterized using liquid chromatography\u2010mass spectrometry to pinpoint specific amino acid residues in close structural proximity. The commonly used lysine\u2010reactive <jats:italic>N<\/jats:italic>\u2010hydroxysuccinimide ester reagents disuccinimidylsuberate (DSS) and bis(sulfosuccinimidyl)suberate (BS<jats:sup>3<\/jats:sup>) have a linker arm that is 11.4 \u00c5 long when fully extended, allowing C<jats:sub>\u03b1<\/jats:sub> (alpha carbon of protein backbone) atoms of crosslinked lysine residues to be up to \u223c24 \u00c5 apart. However, XL\u2010MS studies on proteins of known structure frequently report crosslinks that exceed this distance. Typically, a tolerance of \u223c3 \u00c5 is added to the theoretical maximum to account for this observation, with limited justification for the chosen value. We used the Dynameomics database, a repository of high\u2010quality molecular dynamics simulations of 807 proteins representative of diverse protein folds, to investigate the relationship between lysine\u2013lysine distances in experimental starting structures and in simulation ensembles. We conclude that for DSS\/BS<jats:sup>3<\/jats:sup>, a distance constraint of 26\u201330 \u00c5 between C<jats:sub>\u03b1<\/jats:sub> atoms is appropriate. This analysis provides a theoretical basis for the widespread practice of adding a tolerance to the crosslinker length when comparing XL\u2010MS results to structures or in modeling. We also discuss the comparison of XL\u2010MS results to MD simulations and known structures as a means to test and validate experimental XL\u2010MS methods.<\/jats:p>","DOI":"10.1002\/pro.2458","type":"journal-article","created":{"date-parts":[[2014,3,18]],"date-time":"2014-03-18T09:12:34Z","timestamp":1395133954000},"page":"747-759","source":"Crossref","is-referenced-by-count":314,"title":["Distance restraints from crosslinking mass spectrometry: Mining a molecular dynamics simulation database to evaluate lysine\u2013lysine distances"],"prefix":"10.1002","volume":"23","author":[{"given":"Eric D.","family":"Merkley","sequence":"first","affiliation":[{"name":"Biological Sciences Division Pacific Northwest National Laboratories Richland Washington 99352\u20101793"}]},{"given":"Steven","family":"Rysavy","sequence":"additional","affiliation":[{"name":"Biomedical and Health Informatics Program University of Washington Seattle Washington 98195\u20105013"}]},{"given":"Abdullah","family":"Kahraman","sequence":"additional","affiliation":[{"name":"Institute of Molecular Life Sciences, University of Zurich Winterthurerstrasse 190 8057 Zurich Switzerland"}]},{"given":"Ryan P.","family":"Hafen","sequence":"additional","affiliation":[{"name":"Applied Statistics and Computational Modeling Group Pacific Northwest National Laboratories Richland Washington 99352\u20101793"}]},{"given":"Valerie","family":"Daggett","sequence":"additional","affiliation":[{"name":"Biomedical and Health Informatics Program University of Washington Seattle Washington 98195\u20105013"},{"name":"Department of Bioengineering University of Washington Seattle Washington 98195\u20105013"}]},{"given":"Joshua N.","family":"Adkins","sequence":"additional","affiliation":[{"name":"Biological Sciences Division Pacific Northwest National Laboratories Richland Washington 99352\u20101793"}]}],"member":"311","published-online":{"date-parts":[[2014,4,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts628"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1228565"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/mas.20082"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jms.1762"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2010.10.014"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10969-013-9160-z"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-008-2231-5"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jms.1544"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.090099097"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M110.006841"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr3011638"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2009.401"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00158-10"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1221483"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1120559109"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2103"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1110\/ps.51201"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1110\/ps.052040406"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr1001115"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.2111"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi300064v"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/gzn011"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/gzn015"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/gzn012"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2010.01.012"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq625"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0808-748a"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr100369y"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.6150"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0073411"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr070234i"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac701636w"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/mas.20203"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac101030w"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.565"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13361-011-0288-4"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13361-012-0565-x"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr348"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M111.014126"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2013.03.005"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06522"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.R000001-MCP201"},{"key":"e_1_2_8_44_1","unstructured":".ilmm 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