{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:43:01Z","timestamp":1790167381436,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T00:00:00Z","timestamp":1632960000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In the present in-silico study, various computational techniques were applied to determine potent compounds against TRAP1 kinase. The pharmacophore hypothesis DHHRR_1 consists of important features required for activity. The 3D QSAR study showed a statistically significant model with R2 = 0.96 and Q2 = 0.57. Leave one out (LOO) cross-validation (R2 CV = 0.58) was used to validate the QSAR model. The molecular docking study showed maximum XP docking scores (\u221211.265, \u221210.532, \u221210.422, \u221210.827, \u221210.753 kcal\/mol) for potent pyrazole analogs (42, 46, 49, 56, 43), respectively, with significant interactions with amino acid residues (ASP 594, CYS 532, PHE 583, SER 536) against TRAP1 kinase receptors (PDB ID: 5Y3N). Furthermore, the docking results were validated using the 100 ns MD simulations performed for the selected five docked complexes. The selected inhibitors showed relatively higher binding affinities than the TRAP1 inhibitor molecules present in the literature. The ZINC database was used for a virtual screening study that screened ZINC05297837, ZINC05434822, and ZINC72286418, which showed similar binding interactions to those shown by potent ligands. Absorption, distribution, metabolism, and excretion (ADME) analysis showed noticeable results. The results of the study may be helpful for the further development of potent TRAP1 inhibitors<\/jats:p>","DOI":"10.3390\/molecules26195932","type":"journal-article","created":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T21:23:55Z","timestamp":1633728235000},"page":"5932","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Computational Approaches for the Design of Novel Anticancer Compounds Based on Pyrazolo[3,4-d]pyrimidine Derivatives as TRAP1 Inhibitor"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8463-5182","authenticated-orcid":false,"given":"Amena","family":"Ali","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8562-4749","authenticated-orcid":false,"given":"Magda H.","family":"Abdellattif","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4313-3896","authenticated-orcid":false,"given":"Abuzer","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ola","family":"AbuAli","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd","family":"Shahbaaz","sequence":"additional","affiliation":[{"name":"South African Medical Research Council Bioinformatics Institute, University of Western Cape, Private Bag X17, Bellville, Cape Town 7535, South Africa"},{"name":"Laboratory of Computational Modelling of Drugs, South Ural State University, 76 Lenin Prospects, 454080 Chelyabinsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6919-5489","authenticated-orcid":false,"given":"Mohamed Jawed","family":"Ahsan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Maharishi Arvind College of Pharmacy, Ambabari Circle, Jaipur 302039, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4803-167X","authenticated-orcid":false,"given":"Mostafa A.","family":"Hussien","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia"},{"name":"Department of Chemistry, Faculty of Science, Port Said University, Port Said 42521, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3305","DOI":"10.1074\/jbc.275.5.3305","article-title":"The hsp90-related protein TRAP1 is a mitochondrial protein with distinct functional properties","volume":"275","author":"Felts","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.cell.2007.08.028","article-title":"Regulation of tumor cell mitochondrial homeostasis by an organelle-specific Hsp90 chaperone network","volume":"131","author":"Kang","year":"2007","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Park, H.K., Lee, J.E., Lim, J., Jo, D.E., Park, S.A., Suh, P.G., and Kang, B.H. (2014). 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