{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T09:13:27Z","timestamp":1783761207588,"version":"3.55.0"},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Mol Model"],"published-print":{"date-parts":[[2026,7]]},"DOI":"10.1007\/s00894-026-06823-3","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T05:41:17Z","timestamp":1782366077000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The deformation energy gap in computational drug design: why interaction energy alone cannot rank drug candidates and a thermodynamic correction protocol"],"prefix":"10.1007","volume":"32","author":[{"given":"Iqra","family":"Malik","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2913-1765","authenticated-orcid":false,"given":"Muhammad Javid","family":"Iqbal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"6823_CR1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1713452","volume":"16","author":"MJ Iqbal","year":"2026","unstructured":"Iqbal MJ, Malik I, Bernal G, Salas-Burgos AM, Salazar LA (2026) Computational-experimental integration identifies potent carbohydrate-hydrolyzing enzyme inhibitors from Nardostachys jatamansi: molecular docking, dynamics and pharmacokinetic predictions. Front Pharmacol 16:1713452. https:\/\/doi.org\/10.3389\/fphar.2025.1713452","journal-title":"Front Pharmacol"},{"key":"6823_CR2","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2018.00188","volume":"6","author":"CN Cavasotto","year":"2018","unstructured":"Cavasotto CN, Adler NS, Aucar MG (2018) Quantum chemical approaches in structure-based virtual screening and lead optimization. Front Chem 6:188. https:\/\/doi.org\/10.3389\/fchem.2018.00188","journal-title":"Front Chem"},{"key":"6823_CR3","doi-asserted-by":"publisher","first-page":"4953","DOI":"10.1039\/C4CS00055B","volume":"43","author":"I Fern\u00e1ndez","year":"2014","unstructured":"Fern\u00e1ndez I, Bickelhaupt FM (2014) The activation strain model and molecular orbital theory: understanding and designing chemical reactions. Chem Soc Rev 43:4953\u20134967. https:\/\/doi.org\/10.1039\/C4CS00055B","journal-title":"Chem Soc Rev"},{"key":"6823_CR4","doi-asserted-by":"publisher","first-page":"2499","DOI":"10.1021\/jm030563w","volume":"47","author":"E Perola","year":"2004","unstructured":"Perola E, Charifson PS (2004) Conformational analysis of drug-like molecules bound to proteins: an extensive study of ligand reorganization upon binding. J Med Chem 47:2499\u20132510. https:\/\/doi.org\/10.1021\/jm030563w","journal-title":"J Med Chem"},{"key":"6823_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/9780470125922.ch1","volume-title":"Reviews in computational chemistry","author":"FM Bickelhaupt","year":"2000","unstructured":"Bickelhaupt FM, Baerends EJ (2000) Kohn\u2013Sham density functional theory: predicting and understanding chemistry. In: Lipkowitz KB, Boyd DB (eds) Reviews in computational chemistry, vol 15. Wiley-VCH, New York, pp 1\u201386. https:\/\/doi.org\/10.1002\/9780470125922.ch1"},{"key":"6823_CR6","doi-asserted-by":"publisher","first-page":"1955","DOI":"10.1021\/acs.jmedchem.2c01744","volume":"66","author":"AN Jain","year":"2023","unstructured":"Jain AN, Brueckner AC, Cleves AE, Reibarkh M, Sherer EC (2023) A distributional model of bound ligand conformational strain: from small molecules up to large peptidic macrocycles. J Med Chem 66:1955\u20131971. https:\/\/doi.org\/10.1021\/acs.jmedchem.2c01744","journal-title":"J Med Chem"},{"key":"6823_CR7","doi-asserted-by":"publisher","first-page":"2587","DOI":"10.1002\/jcc.21838","volume":"32","author":"Z Fu","year":"2011","unstructured":"Fu Z, Li X, Merz KM Jr (2011) Accurate assessment of the strain energy in a protein-bound drug using QM\/MM X-ray refinement and converged quantum chemistry. J Comput Chem 32:2587\u20132597. https:\/\/doi.org\/10.1002\/jcc.21838","journal-title":"J Comput Chem"},{"key":"6823_CR8","doi-asserted-by":"publisher","DOI":"10.1002\/jmr.2618","volume":"30","author":"ML Peach","year":"2017","unstructured":"Peach ML, Cachau RE, Nicklaus MC (2017) Conformational energy range of ligands in protein crystal structures: the difficult quest for accurate understanding. J Mol Recognit 30:e2618. https:\/\/doi.org\/10.1002\/jmr.2618","journal-title":"J Mol Recognit"},{"key":"6823_CR9","doi-asserted-by":"publisher","first-page":"2785","DOI":"10.1002\/jcc.21256","volume":"30","author":"GM Morris","year":"2009","unstructured":"Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ (2009) AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem 30:2785\u20132791. https:\/\/doi.org\/10.1002\/jcc.21256","journal-title":"J Comput Chem"},{"key":"6823_CR10","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1002\/wcms.71","volume":"2","author":"M Von Hopffgarten","year":"2012","unstructured":"Von Hopffgarten M, Frenking G (2012) Energy decomposition analysis. WIREs Comput Mol Sci 2:43\u201362. https:\/\/doi.org\/10.1002\/wcms.71","journal-title":"WIREs Comput Mol Sci"},{"key":"6823_CR11","doi-asserted-by":"publisher","first-page":"3785","DOI":"10.1021\/acs.jctc.5b00296","volume":"11","author":"R Sure","year":"2015","unstructured":"Sure R, Grimme S (2015) Comprehensive benchmark of association (free) energies of realistic host\u2013guest complexes. J Chem Theory Comput 11:3785\u20133801. https:\/\/doi.org\/10.1021\/acs.jctc.5b00296","journal-title":"J Chem Theory Comput"},{"key":"6823_CR12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/BF02401406","volume":"46","author":"T Ziegler","year":"1977","unstructured":"Ziegler T, Rauk A (1977) On the calculation of bonding energies by the Hartree\u2013Fock\u2013Slater method. Theor Chim Acta 46:1\u201310. https:\/\/doi.org\/10.1007\/BF02401406","journal-title":"Theor Chim Acta"},{"key":"6823_CR13","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1063\/1.1676210","volume":"55","author":"K Morokuma","year":"1971","unstructured":"Morokuma K (1971) Molecular orbital studies of hydrogen bonds. III. C=O\u00b7\u00b7\u00b7H\u2013O hydrogen bond in H\u2082CO\u00b7\u00b7\u00b7H\u2082O and H\u2082CO\u00b7\u00b7\u00b72H\u2082O. J Chem Phys 55:1236\u20131244. https:\/\/doi.org\/10.1063\/1.1676210","journal-title":"J Chem Phys"},{"key":"6823_CR14","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1080\/00268977000101561","volume":"19","author":"SF Boys","year":"1970","unstructured":"Boys SF, Bernardi F (1970) The calculation of small molecular interactions by the differences of separate total energies. Some procedures with reduced errors. Mol Phys 19:553\u2013566. https:\/\/doi.org\/10.1080\/00268977000101561","journal-title":"Mol Phys"},{"key":"6823_CR15","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1038\/nrd2590","volume":"7","author":"EM Driggers","year":"2008","unstructured":"Driggers EM, Hale SP, Lee J, Terrett NK (2008) The exploration of macrocycles for drug discovery-an underexploited structural class. Nat Rev Drug Discov 7:608\u2013624. https:\/\/doi.org\/10.1038\/nrd2590","journal-title":"Nat Rev Drug Discov"},{"key":"6823_CR16","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1021\/jm400887j","volume":"57","author":"F Giordanetto","year":"2014","unstructured":"Giordanetto F, Kihlberg J (2014) Macrocyclic drugs and clinical candidates: what can medicinal chemists learn from their properties? J Med Chem 57:278\u2013295. https:\/\/doi.org\/10.1021\/jm400887j","journal-title":"J Med Chem"},{"key":"6823_CR17","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1146\/annurev-biophys-070816-033654","volume":"46","author":"DL Mobley","year":"2017","unstructured":"Mobley DL, Gilson MK (2017) Predicting binding free energies: frontiers and benchmarks. Annu Rev Biophys 46:531\u2013558. https:\/\/doi.org\/10.1146\/annurev-biophys-070816-033654","journal-title":"Annu Rev Biophys"}],"container-title":["Journal of Molecular Modeling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00894-026-06823-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00894-026-06823-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00894-026-06823-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T08:50:22Z","timestamp":1783759822000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00894-026-06823-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,25]]},"references-count":17,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["6823"],"URL":"https:\/\/doi.org\/10.1007\/s00894-026-06823-3","relation":{},"ISSN":["1610-2940","0948-5023"],"issn-type":[{"value":"1610-2940","type":"print"},{"value":"0948-5023","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,25]]},"assertion":[{"value":"25 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"240"}}