{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:34:05Z","timestamp":1773275645911,"version":"3.50.1"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"13","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":3015,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/2.0\/uk\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Motivation: The Backrub is a small but kinematically efficient side-chain-coupled local backbone motion frequently observed in atomic-resolution crystal structures of proteins. A backrub shifts the C\u03b1\u2013C\u03b2 orientation of a given side-chain by rigid-body dipeptide rotation plus smaller individual rotations of the two peptides, with virtually no change in the rest of the protein. Backrubs can therefore provide a biophysically realistic model of local backbone flexibility for structure-based protein design. Previously, however, backrub motions were applied via manual interactive model-building, so their incorporation into a protein design algorithm (a simultaneous search over mutation and backbone\/side-chain conformation space) was infeasible.<\/jats:p>\n                  <jats:p>Results: We present a combinatorial search algorithm for protein design that incorporates an automated procedure for local backbone flexibility via backrub motions. We further derive a dead-end elimination (DEE)-based criterion for pruning candidate rotamers that, in contrast to previous DEE algorithms, is provably accurate with backrub motions. Our backrub-based algorithm successfully predicts alternate side-chain conformations from \u22640.9 \u00c5 resolution structures, confirming the suitability of the automated backrub procedure. Finally, the application of our algorithm to redesign two different proteins is shown to identify a large number of lower-energy conformations and mutation sequences that would have been ignored by a rigid-backbone model.<\/jats:p>\n                  <jats:p>Availability: Contact authors for source code.<\/jats:p>\n                  <jats:p>Contact: \u00a0brd+ismb08@cs.duke.edu<\/jats:p>","DOI":"10.1093\/bioinformatics\/btn169","type":"journal-article","created":{"date-parts":[[2008,6,27]],"date-time":"2008-06-27T03:43:13Z","timestamp":1214538193000},"page":"i196-i204","source":"Crossref","is-referenced-by-count":66,"title":["Algorithm for backrub motions in protein design"],"prefix":"10.1093","volume":"24","author":[{"given":"Ivelin","family":"Georgiev","sequence":"first","affiliation":[{"name":"1 Department of Computer Science, Duke University and 2Department of Biochemistry, Duke University Medical Center, Durham, NC 27708, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Keedy","sequence":"additional","affiliation":[{"name":"1 Department of Computer Science, Duke University and 2Department of Biochemistry, Duke University Medical Center, Durham, NC 27708, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane S.","family":"Richardson","sequence":"additional","affiliation":[{"name":"1 Department of Computer Science, Duke University and 2Department of Biochemistry, Duke University Medical Center, Durham, NC 27708, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David C.","family":"Richardson","sequence":"additional","affiliation":[{"name":"1 Department of Computer Science, Duke University and 2Department of Biochemistry, Duke University Medical Center, Durham, NC 27708, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce R.","family":"Donald","sequence":"additional","affiliation":[{"name":"1 Department of Computer Science, Duke University and 2Department of Biochemistry, Duke University Medical Center, Durham, NC 27708, USA"},{"name":"1 Department of Computer Science, Duke University and 2Department of Biochemistry, Duke University Medical Center, Durham, NC 27708, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2008,7,1]]},"reference":[{"key":"2023020210381930200_B1","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1287\/ijoc.1040.0096","article-title":"A semidefinite programming approach to side-chain positioning with new rounding strategies","volume":"16","author":"Chazelle","year":"2004","journal-title":"INFORMS J. 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