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In the absence of high-resolution data, low-resolution information in the form of spatial restraints can significantly contribute to the precision and accuracy of structural models obtained using computational approaches. To obtain such restraints, chemical cross-linking coupled with mass spectrometry (XL-MS) is commonly used. However, the use of XL-MS in the modeling of protein complexes comprised of identical subunits (homo-oligomers) is often hindered by the inherent ambiguity of <jats:italic>intra<\/jats:italic>- and <jats:italic>inter<\/jats:italic>-subunit connection assignment.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We present a comprehensive evaluation of (1) different methods for <jats:italic>inter<\/jats:italic>-residue distance calculations, and (2) different approaches for the scoring of spatial restraints. Our results show that using Solvent Accessible Surface distances (SASDs) instead of Euclidean distances (EUCs) greatly reduces the assignation ambiguity and delivers better modeling precision. Furthermore, ambiguous connections should be considered as <jats:italic>inter<\/jats:italic>-subunit only when the <jats:italic>intra<\/jats:italic>-subunit alternative exceeds the distance threshold. Modeling performance can also be improved if symmetry, characteristic for most homo-oligomers, is explicitly defined in the scoring function.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our findings provide guidelines for proper evaluation of chemical cross-linking-based spatial restraints in modeling homo-oligomeric protein complexes, which could facilitate structural characterization of this important group of proteins.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12859-019-3032-x","type":"journal-article","created":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T13:04:31Z","timestamp":1568034271000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Proper evaluation of chemical cross-linking-based spatial restraints improves the precision of modeling homo-oligomeric protein complexes"],"prefix":"10.1186","volume":"20","author":[{"given":"Alja\u017e","family":"Gaber","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregor","family":"Gun\u010dar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2230-1758","authenticated-orcid":false,"given":"Miha","family":"Pav\u0161i\u010d","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,9,9]]},"reference":[{"key":"3032_CR1","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1126\/science.1228565","volume":"339","author":"AB Ward","year":"2013","unstructured":"Ward AB, Sali A, Wilson IA. 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