{"id":23207,"date":"2025-12-17T17:36:02","date_gmt":"2025-12-17T17:36:02","guid":{"rendered":"https:\/\/scientificassociation.org\/?post_type=journal-paper&#038;p=23207"},"modified":"2025-12-27T14:02:18","modified_gmt":"2025-12-27T14:02:18","slug":"terpene-scaffolds-as-allosteric-inhibitors-of-ptp1b-an-integrated-docking-md-and-mm-pbsa-study","status":"publish","type":"journal-paper","link":"https:\/\/scientificassociation.org\/ar\/journal-paper\/terpene-scaffolds-as-allosteric-inhibitors-of-ptp1b-an-integrated-docking-md-and-mm-pbsa-study\/","title":{"rendered":"Terpene scaffolds as allosteric inhibitors of PTP1B: An integrated docking, MD, and MM\/PBSA study"},"content":{"rendered":"<p>Protein tyrosine phosphatase 1B (PTP1B) is a validated antidiabetic and anti-obesity target whose activity can be attenuated by small molecules engaging an allosteric cleft between helices \u03b13\/\u03b17 beneath the Phe196\/Phe280 \u201caromatic clamp.\u201d Motivated by the tractability of terpene scaffolds, we evaluated artemisinic acid, dehydroabietic acid, and santonin as PTP1B allosteric inhibitors using an integrated in-silico pipeline. The 1T49 crystal structure was prepared and used for structure-based docking, followed by 200-ns explicit-solvent molecular dynamics (MD) and MM\/PBSA end-point free-energy analysis. Docking located all three ligands in the \u03b13\/\u03b17 pocket with predicted affinities of \u22127.6 (artemisinic acid), \u22128.1 (dehydroabietic acid), and \u22128.7 kcal\u00b7mol\u207b\u00b9 (santonin), reproducing the characteristic hydrophobic contacts to Phe196\/Phe280 and polar interactions at the mouth (Asn193\/Lys197\/Glu200). MD indicated stable protein backbones for all complexes, while ligand mobility differentiated the series: the dehydroabietic-acid complex showed the lowest ligand RMSD and most persistent mouth hydrogen bonding; artemisinic acid was intermediate; santonin displayed greater early pose wandering despite favorable docking. MM\/PBSA ranked dehydroabietic acid as the most favorable binder, followed by artemisinic acid, with santonin weakest\u2014consistent with stronger van-der-Waals\/packing and a smaller desolvation penalty for the abietane scaffold. Collectively, the data highlight deep hydrophobic burial against the aromatic clamp, plus one to two mouth-region polar contacts, as the key determinants of allosteric stabilization. Dehydroabietic acid emerges as a promising lead for optimization, with clear vectors to enhance potency while maintaining pocket complementarity. These findings support terpene-derived chemotypes as credible starting points for selective PTP1B allosteric inhibitor design.<\/p>\n","protected":false},"featured_media":23206,"template":"","meta":{"_acf_changed":false},"journal-name":[221],"paper-tag":[232,231],"class_list":["post-23207","journal-paper","type-journal-paper","status-publish","has-post-thumbnail","hentry","journal-name-sasj","paper-tag-issue-2","paper-tag-volume-2"],"acf":[],"_links":{"self":[{"href":"https:\/\/scientificassociation.org\/ar\/wp-json\/wp\/v2\/journal-paper\/23207","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/scientificassociation.org\/ar\/wp-json\/wp\/v2\/journal-paper"}],"about":[{"href":"https:\/\/scientificassociation.org\/ar\/wp-json\/wp\/v2\/types\/journal-paper"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/scientificassociation.org\/ar\/wp-json\/wp\/v2\/media\/23206"}],"wp:attachment":[{"href":"https:\/\/scientificassociation.org\/ar\/wp-json\/wp\/v2\/media?parent=23207"}],"wp:term":[{"taxonomy":"journal-name","embeddable":true,"href":"https:\/\/scientificassociation.org\/ar\/wp-json\/wp\/v2\/journal-name?post=23207"},{"taxonomy":"paper-tag","embeddable":true,"href":"https:\/\/scientificassociation.org\/ar\/wp-json\/wp\/v2\/paper-tag?post=23207"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}