{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T06:31:48Z","timestamp":1768717908769,"version":"3.49.0"},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,1,18]],"date-time":"2019-01-18T00:00:00Z","timestamp":1547769600000},"content-version":"am","delay-in-days":348,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2018,2,4]],"date-time":"2018-02-04T00:00:00Z","timestamp":1517702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM\u2010031749"],"award-info":[{"award-number":["GM\u2010031749"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM\u2010065307"],"award-info":[{"award-number":["GM\u2010065307"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM\u2010103426"],"award-info":[{"award-number":["GM\u2010103426"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:p>Malaria, mainly caused by <jats:italic>Plasmodium falciparum<\/jats:italic> and <jats:italic>Plasmodium vivax,<\/jats:italic> has been a growing cause of morbidity and mortality. <jats:italic>P.\u00a0falciparum<\/jats:italic> is more lethal than is <jats:italic>P.\u00a0vivax<\/jats:italic>, but there is a vital need for effective drugs against both species. Geranylgeranyl diphosphate synthase (<jats:styled-content style=\"fixed-case\">GGPPS<\/jats:styled-content>) is an enzyme involved in the biosynthesis of quinones and in protein prenylation and has been proposed to be a malaria drug target. However, the structure of <jats:italic>P.\u00a0falciparum<\/jats:italic><jats:styled-content style=\"fixed-case\">GGPPS<\/jats:styled-content> (<jats:italic>Pf<\/jats:italic><jats:styled-content style=\"fixed-case\">GGPPS<\/jats:styled-content>) has not been determined, due to difficulties in crystallization. Here, we created a <jats:italic>Pf<\/jats:italic><jats:styled-content style=\"fixed-case\">GGPPS<\/jats:styled-content> model using the homologous <jats:italic>P.vivax<\/jats:italic><jats:styled-content style=\"fixed-case\">GGPPS<\/jats:styled-content> X\u2010ray structure as a template. We simulated the modeled <jats:italic>Pf<\/jats:italic><jats:styled-content style=\"fixed-case\">GGPPS<\/jats:styled-content> as well as <jats:italic>Pv<\/jats:italic><jats:styled-content style=\"fixed-case\">GGPPS<\/jats:styled-content> using conventional and Gaussian accelerated molecular dynamics in both <jats:italic>apo\u2010<\/jats:italic> and <jats:styled-content style=\"fixed-case\">GGPP<\/jats:styled-content>\u2010bound states. The <jats:styled-content style=\"fixed-case\">MD<\/jats:styled-content> simulations revealed a striking similarity in the dynamics of both enzymes with loop 9\u201010 controlling access to the active site. We also found that <jats:styled-content style=\"fixed-case\">GGPP<\/jats:styled-content> stabilizes <jats:italic>Pf<\/jats:italic><jats:styled-content style=\"fixed-case\">GGPPS<\/jats:styled-content> and <jats:italic>Pv<\/jats:italic><jats:styled-content style=\"fixed-case\">GGPPS<\/jats:styled-content> into closed conformations and <jats:italic>via<\/jats:italic> similar mechanisms. Shape\u2010based analysis of the binding sites throughout the simulations suggests that the two enzymes will be readily targeted by the same inhibitors. Finally, we produced three <jats:styled-content style=\"fixed-case\">MD<\/jats:styled-content>\u2010validated conformations of <jats:italic>Pf<\/jats:italic><jats:styled-content style=\"fixed-case\">GGPPS<\/jats:styled-content> to be used in future virtual screenings for potential new antimalarial drugs acting on both <jats:italic>Pv<\/jats:italic><jats:styled-content style=\"fixed-case\">GGPPS<\/jats:styled-content> and <jats:italic>Pf<\/jats:italic><jats:styled-content style=\"fixed-case\">GGPPS<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/cbdd.13170","type":"journal-article","created":{"date-parts":[[2018,1,18]],"date-time":"2018-01-18T09:02:30Z","timestamp":1516266150000},"page":"1068-1077","source":"Crossref","is-referenced-by-count":6,"title":["Remarkable similarity in <i>Plasmodium falciparum<\/i> and <i>Plasmodium vivax<\/i> geranylgeranyl diphosphate synthase dynamics and its implication for antimalarial drug design"],"prefix":"10.1111","volume":"91","author":[{"given":"Aishwarya","family":"Venkatramani","sequence":"first","affiliation":[{"name":"Department of Pharmacology University of California at San Diego  La Jolla CA USA"},{"name":"Department of Chemistry and Biochemistry University of California at San Diego  La Jolla CA USA"},{"name":"National Biomedical Computation Resource University of California at San Diego  La Jolla CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3289-2248","authenticated-orcid":false,"given":"Clarisse","family":"Gravina Ricci","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of California at San Diego  La Jolla CA USA"},{"name":"Department of Chemistry and Biochemistry University of California at San Diego  La Jolla CA USA"},{"name":"National Biomedical Computation Resource University of California at San Diego  La Jolla CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Oldfield","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Illinois at Urbana\u2010Champaign  Urbana IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Andrew","family":"McCammon","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of California at San Diego  La Jolla CA USA"},{"name":"Department of Chemistry and Biochemistry University of California at San Diego  La Jolla CA USA"},{"name":"National Biomedical Computation Resource University of California at San Diego  La Jolla CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,2,4]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"WHO 2016."},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2331"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161213804070302"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2016.1195537"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm8009074"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00198-10"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1118215109"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.6b00398"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.5b00436"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw1099"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(05)80360-2"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku340"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.197"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bti770"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp322"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks375"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.20922"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki464"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh381"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm276"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20290"},{"key":"e_1_2_8_23_1","volume-title":"AMBER14","author":"Case D. A.","year":"2014"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.5b00255"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.445869"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9991(77)90098-5"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.464397"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.470117"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/ct400341p"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0263-7855(96)00018-5"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmre.2001.2300"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.7b00500"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/ct4010454"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2016.01.005"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja210751t"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004578"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja0723535"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi300561n"}],"container-title":["Chemical Biology &amp; Drug Design"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcbdd.13170","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.13170","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cbdd.13170","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/am-pdf\/10.1111\/cbdd.13170","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.13170","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T19:08:48Z","timestamp":1695496128000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cbdd.13170"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,4]]},"references-count":37,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,6]]}},"alternative-id":["10.1111\/cbdd.13170"],"URL":"https:\/\/doi.org\/10.1111\/cbdd.13170","archive":["Portico"],"relation":{},"ISSN":["1747-0277","1747-0285"],"issn-type":[{"value":"1747-0277","type":"print"},{"value":"1747-0285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,4]]}}}