{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T14:12:51Z","timestamp":1737123171740,"version":"3.33.0"},"reference-count":20,"publisher":"Begell House","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Crit Rev Oncog"],"published-print":{"date-parts":[[2025]]},"abstract":"<p>The heat shock protein 90 kDa (HSP90) is highly conserved across diverse species, including humans, and upregulated in various cancers. As a result, it has been identified as a promising target for advancing anticancer medicine. The introduction of combinatorial chemistry in drug discovery has emphasized the need to develop new technologies in screening, designing, decoding, synthesizing, and screening combinatorial drug libraries. The current investigation was carried out to report improved inhibition efficacy of ganetespib, fluorouracil (5-FU), and its combinatorial drug treatment (ganetespib + 5-FU) against the HSP90 molecular chaperone through an &lt;i&gt;in silico&lt;\/i&gt; approach. Both drugs and their combination are ATP-competitive inhibitors; they inhibit the HSP90&amp;alpha; N-terminal and block the ATP binding site. The structural and functional basis and their combination were confirmed through molecular docking interaction with HSP90&amp;alpha;. The inhibitors' conformational effects and their combination against the HSP90&amp;alpha; protein were studied using powerful MD simulations. The key interacting residues of HSP90&amp;alpha; with ganetespib, 5-FU, and ganetespib + 5-FU were identified via energy binding calculations and molecular dynamics. This study is the first to offer atomistic insights into the interaction between ganetespib, 5-FU, and ganetespib + 5-FU with the HSP90&amp;alpha; protein N-terminal domain. The results of our &lt;i&gt;in silico&lt;\/i&gt; study will open better avenues for developing potential cancer inhibitors in the near future.\n<\/p>","DOI":"10.1615\/critrevoncog.2024056394","type":"journal-article","created":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T19:09:47Z","timestamp":1728587387000},"page":"31-42","source":"Crossref","is-referenced-by-count":0,"title":["Interaction of Heat Shock Protein 90 (HSP90), Ganetespib, and 5-Fluorouracil by Computational Approach for Colorectal Cancer Therapy"],"prefix":"10.1615","volume":"30","author":[{"given":"Yuvasri","family":"Golivi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santosh Kumar","family":"Behera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Afroz","family":"Alam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sujatha","family":"Peela","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"613","reference":[{"key":"2","doi-asserted-by":"crossref","unstructured":"Hu C, Yang J, Qi Z, Wu H, Wang B, Zou F, Mei H, Liu J, Wang W, Liu Q. 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