{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T06:54:58Z","timestamp":1774508098447,"version":"3.50.1"},"reference-count":93,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T00:00:00Z","timestamp":1738540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioinform."],"abstract":"<jats:p>Proteins, composed of amino acids, are crucial for a wide range of biological functions. Proteins have various interaction sites, one of which is the protein-ligand binding site, essential for molecular interactions and biochemical reactions. These sites enable proteins to bind with other molecules, facilitating key biological functions. Accurate prediction of these binding sites is pivotal in computational drug discovery, helping to identify therapeutic targets and facilitate treatment development. Machine learning has made significant contributions to this field by improving the prediction of protein-ligand interactions. This paper reviews studies that use machine learning to predict protein-ligand binding sites from sequence data, focusing on recent advancements. The review examines various embedding methods and machine learning architectures, addressing current challenges and the ongoing debates in the field. Additionally, research gaps in the existing literature are highlighted, and potential future directions for advancing the field are discussed. This study provides a thorough overview of sequence-based approaches for predicting protein-ligand binding sites, offering insights into the current state of research and future possibilities.<\/jats:p>","DOI":"10.3389\/fbinf.2025.1520382","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T06:34:35Z","timestamp":1738564475000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Machine learning approaches for predicting protein-ligand binding sites from sequence data"],"prefix":"10.3389","volume":"5","author":[{"given":"Orhun","family":"Vural","sequence":"first","affiliation":[]},{"given":"Leon","family":"Jololian","sequence":"additional","affiliation":[]}],"member":"1965","published-online":{"date-parts":[[2025,2,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1038\/s41589-024-01638-w","article-title":"The power and pitfalls of AlphaFold2 for structure prediction beyond rigid globular proteins","volume":"20","author":"Agarwal","year":"2024","journal-title":"Nat. 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