{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T08:36:04Z","timestamp":1776760564855,"version":"3.51.2"},"reference-count":13,"publisher":"World Scientific Pub Co Pte Ltd","issue":"02","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Bioinform. Comput. Biol."],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:p>In this paper, we develop a connectivity-exact bond-resolved framework for quantifying structural accessibility and persistence in drug molecules. Representing a molecule as a heavy-atom graph [Formula: see text] each bond is classified uniquely as either a connectivity-critical Entry-point bond ([Formula: see text]) or a connectivity-preserving Fortress bond ([Formula: see text]) yielding the exact identity [Formula: see text] This exhaustive partition separates fragmentation capacity from invariant scaffold structure without adjustable parameters. To refine the invariance coordinate we introduce Total Structural Entrenchment (TSE) a persistence-weighted functional defined over cycle-supported bonds and modulated by local steric wall contributions [Formula: see text]. The resulting two-parameter embedding [Formula: see text] distinguishes superficial cyclic extent from deeply embedded structural reinforcement and resolves degeneracies inherent in raw bond counts. Metabolic progression is formalized as recursive bridge depletion generating a directed migration across the architectural plane toward a bridge-depleted refractory core. Within this framework scaffold persistence is interpreted as a connectivity-driven contraction governed strictly by graph topology. The resulting invariance\u2013variation embedding establishes a mathematically controlled bond-level representation of structural accessibility and cyclic entrenchment.<\/jats:p>","DOI":"10.1142\/s0219720026710010","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T07:38:27Z","timestamp":1776757107000},"source":"Crossref","is-referenced-by-count":0,"title":["Bond-resolved graph-theoretic modeling of structural invariance and metabolic accessibility in drug molecules"],"prefix":"10.1142","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8989-5462","authenticated-orcid":false,"given":"K. Nalini","family":"Devi","sequence":"first","affiliation":[{"name":"Department of Mathematics, Government First Grade College, K. R. Pura, Bangalore 560036, Karnataka, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0315-9423","authenticated-orcid":false,"given":"G.","family":"Srinivasa","sequence":"additional","affiliation":[{"name":"Department of Mathematics, New Horizon College of Engineering, Bengaluru 560103, Karnataka, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"219","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"S0219720026710010BIB001","doi-asserted-by":"publisher","DOI":"10.1021\/tx700079z"},{"key":"S0219720026710010BIB002","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.200790032"},{"key":"S0219720026710010BIB003","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2012.12.007"},{"key":"S0219720026710010BIB004","first-page":"1","volume":"196","author":"Williams JA","year":"2010","journal-title":"Handb Exp Pharmacol"},{"issue":"12","key":"S0219720026710010BIB005","first-page":"811","volume":"17","author":"Smith DA","year":"2018","journal-title":"Nat Rev Drug Discov"},{"issue":"6","key":"S0219720026710010BIB006","first-page":"114","volume":"28","author":"Kirchmair J","year":"2015","journal-title":"Chem Res Toxicol"},{"issue":"6","key":"S0219720026710010BIB007","first-page":"1241","volume":"47","author":"Lombardo F","year":"2004","journal-title":"J Med Chem"},{"key":"S0219720026710010BIB008","volume-title":"Chemical Graph Theory","author":"Trinajsti\u0107 N","year":"1992","edition":"2"},{"key":"S0219720026710010BIB009","volume-title":"The Structure of Complex Networks: Theory and Applications","author":"Estrada E","year":"2012"},{"key":"S0219720026710010BIB010","doi-asserted-by":"publisher","DOI":"10.1021\/jm4004285"},{"key":"S0219720026710010BIB011","doi-asserted-by":"publisher","DOI":"10.1002\/bies.10385"},{"key":"S0219720026710010BIB012","doi-asserted-by":"publisher","DOI":"10.1021\/ci00047a033"},{"issue":"1","key":"S0219720026710010BIB013","first-page":"119","volume":"43","author":"Bonchev D","year":"2003","journal-title":"J Chem Inf Comput Sci"}],"container-title":["Journal of Bioinformatics and Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.worldscientific.com\/doi\/pdf\/10.1142\/S0219720026710010","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T07:38:37Z","timestamp":1776757117000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.worldscientific.com\/doi\/10.1142\/S0219720026710010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":13,"journal-issue":{"issue":"02","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1142\/S0219720026710010"],"URL":"https:\/\/doi.org\/10.1142\/s0219720026710010","relation":{},"ISSN":["0219-7200","1757-6334"],"issn-type":[{"value":"0219-7200","type":"print"},{"value":"1757-6334","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"article-number":"2671001"}}