{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T22:55:42Z","timestamp":1762642542397,"version":"3.37.3"},"reference-count":48,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T00:00:00Z","timestamp":1624406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100007446","name":"King Khalid University","doi-asserted-by":"publisher","award":["Deanship of Scientific Research","(R.G.P.1\/333\/42)"],"award-info":[{"award-number":["Deanship of Scientific Research","(R.G.P.1\/333\/42)"]}],"id":[{"id":"10.13039\/501100007446","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Past several decades, therapeutic investigations lead to the discovery of numerous antihypertensive drugs. Although it has been proved for their potency, altered efficacy is common norms in several conditions due to genetic variations. Cytochrome P450 plays a crucial role in drug metabolism and responsible for the pharmacokinetic and pharmacodynamic properties of the drug molecules. Here, we report the deleterious point mutations in the genes associated with the altered response of antihypertensive drug molecules and their metabolizers. Missense variants were filtered as potential nonsynonymous single nucleotide polymorphisms among the available data for the target genes (<jats:italic>REN, CYP2D6, CYP3A4<\/jats:italic>). The key objective of the work is to identify the deleterious single nucleotide polymorphisms (SNPs) responsible for the drug response and metabolism for the application of personalized medication. The molecular docking studies revealed that Aliskiren and other clinically approved drug molecules have a high binding affinity with both wild and mutant structures of renin, CYP2D6, and CYP3A4 proteins. The docking (Glide XP) score was observed to have in the range of \u22128.896 to \u221211.693\u2009kcal\/mol. The molecular dynamics simulation studies were employed to perceive the structural changes and conformational deviation through various analyses. Each studied SNPs was observed to have disparate scoring in the binding affinity to the specific drug molecules. As a prospective plan, we assume this study might be applied to identify the risky SNPs associated with hypertension from the patients to recommend the suitable drug for personalized hypertensive treatment. Further, extensive clinical pharmacogenomics studies are required to support the findings.<\/jats:p>","DOI":"10.1002\/jcb.30069","type":"journal-article","created":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T19:29:37Z","timestamp":1624476577000},"page":"1460-1474","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Mechanistic insights on nsSNPs on binding site of renin and cytochrome P450 proteins: A computational perceptual study for pharmacogenomics evaluation"],"prefix":"10.1002","volume":"122","author":[{"given":"Lakshmanan","family":"Loganathan","sequence":"first","affiliation":[{"name":"Department of Bioinformatics Alagappa University Karaikudi Tamil Nadu India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beena Briget","family":"Kuriakose","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Applied Medical Sciences King Khalid University Khamis Mushayt Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sakeena","family":"Mushfiq","sequence":"additional","affiliation":[{"name":"Department of Public Health, College of Applied Medical Sciences King Khalid University Khamis Mushayt Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7755-3381","authenticated-orcid":false,"given":"Karthikeyan","family":"Muthusamy","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics Alagappa University Karaikudi Tamil Nadu India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,6,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.9692.1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000008331"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0169258"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29060"},{"key":"e_1_2_9_6_1","first-page":"65","article-title":"Computational study of ACE and AGT gene of RAAS pathway","volume":"19","author":"Gautam N","year":"2018","journal-title":"World News Nat Sci"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.18553\/jmcp.2007.13.s8-b.21"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1592\/phco.29.2.193"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/1423-0127-16-42"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gheart.2017.01.006"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(03)00670-X"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.115.06345"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2008.11.018"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.312579"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(02)01363-3"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2007.02.014"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000000773"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612820666141024151119"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2019.103583"},{"issue":"4","key":"e_1_2_9_20_1","doi-asserted-by":"crossref","first-page":"e0174953","DOI":"10.1371\/journal.pone.0174953","article-title":"Determining the role of missense mutations in the POU domain of HNF1A that reduce the DNA\u2010binding affinity: a computational approach","volume":"12","author":"Sneha P","year":"2017","journal-title":"PLoS One"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep37284"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3109\/10799893.2014.922575"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-7364-7-10"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2020.1742790"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw361"},{"key":"e_1_2_9_27_1","first-page":"2018","volume-title":"Schr\u00f6dinger Release 2018\u20104","author":"Schr\u00f6dinger","year":"2018"},{"issue":"1","key":"e_1_2_9_28_1","first-page":"451","article-title":"Direct renin inhibition\u2014a promising strategy for renal protection?","volume":"19","author":"Lizakowski S","year":"2013","journal-title":"Med Sci Monit"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jash.2010.06.006"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2020.1758787"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.20252"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkf436"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts199"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki370"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2018.1521748"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570180815666180827113622"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5RA14693C"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci500020m"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1517\/17460441.2015.1032936"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10822-013-9644-8"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2013.129"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20566"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.26444"},{"key":"e_1_2_9_44_1","unstructured":"QikProp. (2013). (Version 3.8). New York NS LLC.https:\/\/www.schrodinger.com\/products\/qikprop. Accessed May 20 2021."},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci500161d"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molliq.2021.116204"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.27538"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmgm.2012.11.011"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389450120666190808101356"}],"container-title":["Journal of Cellular Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.30069","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcb.30069","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.30069","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T20:58:12Z","timestamp":1693342692000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcb.30069"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,23]]},"references-count":48,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1002\/jcb.30069"],"URL":"https:\/\/doi.org\/10.1002\/jcb.30069","archive":["Portico"],"relation":{},"ISSN":["0730-2312","1097-4644"],"issn-type":[{"type":"print","value":"0730-2312"},{"type":"electronic","value":"1097-4644"}],"subject":[],"published":{"date-parts":[[2021,6,23]]},"assertion":[{"value":"2021-04-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}