{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:04:12Z","timestamp":1790838252934,"version":"4.1.0"},"reference-count":40,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T00:00:00Z","timestamp":1745366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Computational methods have transformed target and drug discovery, significantly accelerating the identification of biological targets and lead compounds. Despite its limitations, in silico molecular docking represents a foundational tool. Molecular Dynamics (MD) simulations, employing accurate force fields, provide near-realistic insights into a compound\u2019s behavior within a biological target. However, docking and MD predictions may be unreliable without precise knowledge of the target binding site. Through MD simulations, we investigated 100 co-crystal structures of biological targets complexed with active compounds, identifying key structural and energy dynamic features that govern target\u2013ligand interactions. Our analysis provides a detailed quantitative description of these parameters, offering critical validation for improving the predictive reliability of docking and MD simulations. This work provides a robust framework for refining early-stage drug discovery and target identification.<\/jats:p>","DOI":"10.3390\/ijms26093971","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T03:43:37Z","timestamp":1745379817000},"page":"3971","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Unveiling Dynamic Hotspots in Protein\u2013Ligand Binding: Accelerating Target and Drug Discovery Approaches"],"prefix":"10.3390","volume":"26","author":[{"given":"Alfonso","family":"Trezza","sequence":"first","affiliation":[{"name":"ONE-HEALTH Laboratory, Department of Biotechnology Chemistry Pharmacy, University of Siena, Via Aldo Moro, 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9281-034X","authenticated-orcid":false,"given":"Anna","family":"Visibelli","sequence":"additional","affiliation":[{"name":"ONE-HEALTH Laboratory, Department of Biotechnology Chemistry Pharmacy, University of Siena, Via Aldo Moro, 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0009-4011","authenticated-orcid":false,"given":"Bianca","family":"Roncaglia","sequence":"additional","affiliation":[{"name":"ONE-HEALTH Laboratory, Department of Biotechnology Chemistry Pharmacy, University of Siena, Via Aldo Moro, 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2750-7082","authenticated-orcid":false,"given":"Roberta","family":"Barletta","sequence":"additional","affiliation":[{"name":"ONE-HEALTH Laboratory, Department of Biotechnology Chemistry Pharmacy, University of Siena, Via Aldo Moro, 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Iannielli","sequence":"additional","affiliation":[{"name":"ONE-HEALTH Laboratory, Department of Biotechnology Chemistry Pharmacy, University of Siena, Via Aldo Moro, 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5154-5535","authenticated-orcid":false,"given":"Linta","family":"Mahboob","sequence":"additional","affiliation":[{"name":"ONE-HEALTH Laboratory, Department of Biotechnology Chemistry Pharmacy, University of Siena, Via Aldo Moro, 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0263-7107","authenticated-orcid":false,"given":"Ottavia","family":"Spiga","sequence":"additional","affiliation":[{"name":"ONE-HEALTH Laboratory, Department of Biotechnology Chemistry Pharmacy, University of Siena, Via Aldo Moro, 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6976-9086","authenticated-orcid":false,"given":"Annalisa","family":"Santucci","sequence":"additional","affiliation":[{"name":"ONE-HEALTH Laboratory, Department of Biotechnology Chemistry Pharmacy, University of Siena, Via Aldo Moro, 2, 53100 Siena, Italy"},{"name":"SienabioACTIVE, University of Siena, Via Aldo Moro, 2, 53100 Siena, Italy"},{"name":"MetabERN, University of Siena, Via Aldo Moro, 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,23]]},"reference":[{"key":"ref_1","first-page":"1010","article-title":"Molecular docking and structure-based drug design strategies","volume":"20","author":"Ferreira","year":"2015","journal-title":"Drug Discov. 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