{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T16:56:08Z","timestamp":1788368168501,"version":"build-2803163510"},"reference-count":52,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T00:00:00Z","timestamp":1778284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003443","name":"The Ministry of Education and Science of the Russian Federation","doi-asserted-by":"crossref","award":["1024081900029-8"],"award-info":[{"award-number":["1024081900029-8"]}],"id":[{"id":"10.13039\/501100003443","id-type":"DOI","asserted-by":"crossref"}]},{"award":["1024081900029-8"],"award-info":[{"award-number":["1024081900029-8"]}],"id":[{"id":"https:\/\/ror.org\/00ghqgy32","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Selective inhibition of poly(ADP-ribose) polymerase 1 (PARP1) may reduce the hematologic toxicity associated with dual PARP1\/PARP2 inhibition. We performed molecular dynamics simulations for five selective inhibitors in complexes with PARP1 and PARP2, using three independent 50 ns runs per complex after docking and equilibration, followed by protein\u2013ligand interaction fingerprint and statistical analyses. All complexes remained dynamically stable, with ligand root-mean-square deviation values generally within 0.3 nm. Comparative analysis identified three \u03b1F-helix residue pairs with nominally reduced interaction frequencies in PARP2: Asn767\/Ala336, Leu769\/Gly338, and Asp770\/Asp339 (p &lt; 0.05). After Benjamini\u2013Hochberg correction for multiple comparisons, Leu769\/Gly338 remained significant (q &lt; 0.05), indicating that this pair represents the most statistically robust interaction difference within this region. Using palacaparib as the most selective inhibitor, these differences were associated with weakened or lost hydrophobic, van der Waals, and cation\u2013\u03c0 interactions in PARP2. Selective binding of modern PARP1 inhibitors appears to be associated with \u03b1F-helix-dependent interaction patterns, providing a mechanistic basis for the rational design of next-generation selective inhibitors with improved selectivity and potentially reduced toxicity.<\/jats:p>","DOI":"10.3390\/molecules31101592","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T12:05:22Z","timestamp":1778501122000},"page":"1592","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Structural Determinants of PARP1 Selectivity from Molecular Dynamics Analysis of PARP1 and PARP2 Complexes"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3336-4815","authenticated-orcid":false,"given":"Dmitrii O.","family":"Shkil","sequence":"first","affiliation":[{"name":"Institute of Future Biophysics, Institutsky Lane, 9, Dolgoprudny 141700, Moscow Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia A.","family":"Chesnokova","sequence":"additional","affiliation":[{"name":"Institute of Future Biophysics, Institutsky Lane, 9, Dolgoprudny 141700, Moscow Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey A.","family":"Ivashchenko","sequence":"additional","affiliation":[{"name":"Institute of Future Biophysics, Institutsky Lane, 9, Dolgoprudny 141700, Moscow Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8150-7553","authenticated-orcid":false,"given":"Elena V.","family":"Petersen","sequence":"additional","affiliation":[{"name":"Institute of Future Biophysics, Institutsky Lane, 9, Dolgoprudny 141700, Moscow Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp Y.","family":"Maximov","sequence":"additional","affiliation":[{"name":"Institute of Future Biophysics, Institutsky Lane, 9, Dolgoprudny 141700, Moscow Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1615\/CritRevEukaryotGeneExpr.2013006875","article-title":"Review of poly (ADP-ribose) polymerase (PARP) mechanisms of action and rationale for targeting in cancer and other diseases","volume":"24","author":"Morales","year":"2014","journal-title":"Crit. 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