{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:38:06Z","timestamp":1787168286099,"version":"build-2736575974"},"reference-count":27,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,1,23]],"date-time":"2018-01-23T00:00:00Z","timestamp":1516665600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1160060"],"award-info":[{"award-number":["1160060"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2018,5]]},"abstract":"\n Laulimalide (\n LAU<\/jats:styled-content>\n ) and Peloruside A (\n PLA<\/jats:styled-content>\n ) are non\u2010taxane microtubule stabilizing agents with promising antimitotic properties. These ligands promote the assembly of microtubules (\n MT<\/jats:styled-content>\n s) by targeting a unique binding site on \u03b2\u2010tubulin. The X\u2010ray structure for\n LAU<\/jats:styled-content>\n \/\n PLA<\/jats:styled-content>\n \u2010tubulin association was recently elucidated, but little information is available regarding the role of these ligands as modulators of interdimeric interactions across\n MT<\/jats:styled-content>\n s. Herein, we report the use of molecular dynamics (\n MD<\/jats:styled-content>\n ), principal component analysis (\n PCA<\/jats:styled-content>\n ),\n MM<\/jats:styled-content>\n \/\n GBSA<\/jats:styled-content>\n \u2010binding free energy calculations, and computational alanine scanning mutagenesis (\n ASM<\/jats:styled-content>\n ) to examine effect of\n LAU<\/jats:styled-content>\n \/\n PLA<\/jats:styled-content>\n association on lateral and longitudinal contacts between tubulin dimers in reduced\n MT<\/jats:styled-content>\n models.\n MD<\/jats:styled-content>\n and\n PCA<\/jats:styled-content>\n results revealed that\n LAU<\/jats:styled-content>\n \/\n PLA<\/jats:styled-content>\n exerts a strong restriction of lateral and longitudinal interdimeric motions, thus enabling the stabilization of the\n MT<\/jats:styled-content>\n lattice. Besides structural effects,\n LAU<\/jats:styled-content>\n \/\n PLA<\/jats:styled-content>\n induces a substantial strengthening of longitudinal interdimeric interactions, whereas lateral contacts are less affected by these ligands, as revealed by\n MM<\/jats:styled-content>\n \/\n GBSA<\/jats:styled-content>\n and\n ASM<\/jats:styled-content>\n calculations. These results are valuable to increase understanding about the molecular features involved in\n MT<\/jats:styled-content>\n stabilization by\n LAU<\/jats:styled-content>\n \/\n PLA<\/jats:styled-content>\n , and to design novel compounds capable of emulating the mode of action of these ligands.\n <\/jats:p>","DOI":"10.1111\/cbdd.13168","type":"journal-article","created":{"date-parts":[[2018,1,9]],"date-time":"2018-01-09T23:00:14Z","timestamp":1515538814000},"page":"1042-1055","source":"Crossref","is-referenced-by-count":9,"title":["Modulation of lateral and longitudinal interdimeric interactions in microtubule models by Laulimalide and Peloruside A association: A molecular modeling approach on the mechanism of microtubule stabilizing agents"],"prefix":"10.1111","volume":"91","author":[{"given":"Mat\u00edas A.","family":"Z\u00fa\u00f1iga","sequence":"first","affiliation":[{"name":"Departamento de Ciencias Qu\u00edmicas Facultad de Ciencias Exactas Universidad Andres Bello Talcahuano Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel B.","family":"Alderete","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica Facultad de Ciencias Qu\u00edmicas Universidad de Concepci\u00f3n Concepci\u00f3n Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonzalo A.","family":"Ja\u00f1a","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Qu\u00edmicas Facultad de Ciencias Exactas Universidad Andres Bello Talcahuano Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro A.","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Faculdade de Ciencias Universidad do Porto Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J.","family":"Ramos","sequence":"additional","affiliation":[{"name":"Faculdade de Ciencias Universidad do Porto Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6783-5657","authenticated-orcid":false,"given":"Ver\u00f3nica A.","family":"Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Qu\u00edmicas Facultad de Ciencias Exactas Universidad Andres Bello Talcahuano Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,1,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm4084"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2013.01.014"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1317"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201307749"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2017.01.001"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.12595"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiolchem.2015.02.018"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.13046"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/1062936X.2015.1070200"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.25087"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10822-017-0029-2"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.12475"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2015.1078115"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2014.05.047"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004313"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1110\/ps.03187503"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku340"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks375"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki464"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.10128"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/ct300418h"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.106.089987"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-658-0_11"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.108.129072"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2008.03.026"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.03.053"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2010.04.038"}],"container-title":["Chemical Biology & Drug Design"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcbdd.13168","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.13168","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,16]],"date-time":"2023-09-16T15:12:02Z","timestamp":1694877122000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cbdd.13168"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,23]]},"references-count":27,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018,5]]}},"alternative-id":["10.1111\/cbdd.13168"],"URL":"https:\/\/doi.org\/10.1111\/cbdd.13168","archive":["Portico"],"relation":{},"ISSN":["1747-0277","1747-0285"],"issn-type":[{"value":"1747-0277","type":"print"},{"value":"1747-0285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,23]]}}}