{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:47:09Z","timestamp":1788871629549,"version":"build-2803163510"},"reference-count":56,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2011,8,23]],"date-time":"2011-08-23T00:00:00Z","timestamp":1314057600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Ruth Kirschstein Graduate Research Fellowship","award":["GM081901"],"award-info":[{"award-number":["GM081901"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Proteins"],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Point deletions in enzymes can vary in effect from negligible to complete loss of activity; however, these effects are not generally predictable. Deletions are widely observed in nature and often result in diseases such as cancer, cystic fibrosis, or osteogenesis imperfecta. Here, we have developed an algorithm to model the perturbed structures of deletion mutants with the ultimate goal of predicting their activities. The algorithm works by deleting the specified residue from the wild\u2010type structure, creating a gap that is closed using a combination of local and global moves that change the backbone torsion angles of the protein structure. On a set of five proteins for which both wild\u2010type and deletion mutant x\u2010ray crystal structures are available, the algorithm produces deep, narrow energy funnels within 1.5 \u00c5 of the crystal structure for the deletion mutants. To assess the ability of our algorithm to predict activity from the predicted structures, we tested the correlation of experimental activity with several measures of the predicted structure ensemble using a set of 45 point deletions from ricin. Estimates incorporating likely prevalence of active and inactive deletion sites suggest that activity can be predicted correctly over 60% of the time from the active site root\u2010mean squared deviation of the lowest energy predicted structures. The predictions are stronger than simple sequence organization measures, but more fundamental work is required in structure prediction and enzyme activity determination to allow consistent prediction of activity. Proteins 2011; \u00a9 2011 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/prot.23109","type":"journal-article","created":{"date-parts":[[2011,7,11]],"date-time":"2011-07-11T10:18:48Z","timestamp":1310379528000},"page":"2844-2860","source":"Crossref","is-referenced-by-count":9,"title":["Computed structures of point deletion mutants and their enzymatic activities"],"prefix":"10.1002","volume":"79","author":[{"given":"Monica","family":"Berrondo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey J.","family":"Gray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,8,23]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0958-1669(95)80067-0"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(03)01308-5"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.212627499"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.235"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6769-7-1"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.51.30581"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2007.07.018"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gnh135"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00132a025"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1113801"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki615"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444908020039"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.21636"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06249"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.20729"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7007-5-17"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1152692"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06879"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.2144\/000112336"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0607691103"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/stke.2192004pl2"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/12.7.549"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(02)00442-4"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.0030164"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2000.3889"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.21453"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6807-7-54"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.21115"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl190"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.4510"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0305043101"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1997.0959"},{"key":"e_1_2_6_34_2","series-title":"Protein structure prediction using Rosetta. 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