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Structure prediction of protein-ligand complexes from sequence information with Umol
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab). Freie Universität Berlin, Germany.ORCID iD: 0000-0003-3439-1866
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Number of Authors: 52024 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 15, article id 4536Article in journal (Refereed) Published
Abstract [en]

Protein-ligand docking is an established tool in drug discovery and development to narrow down potential therapeutics for experimental testing. However, a high-quality protein structure is required and often the protein is treated as fully or partially rigid. Here we develop an AI system that can predict the fully flexible all-atom structure of protein-ligand complexes directly from sequence information. We find that classical docking methods are still superior, but depend upon having crystal structures of the target protein. In addition to predicting flexible all-atom structures, predicted confidence metrics (plDDT) can be used to select accurate predictions as well as to distinguish between strong and weak binders. The advances presented here suggest that the goal of AI-based drug discovery is one step closer, but there is still a way to go to grasp the complexity of protein-ligand interactions fully. Umol is available at: https://github.com/patrickbryant1/Umol.

Place, publisher, year, edition, pages
2024. Vol. 15, article id 4536
National Category
Medicinal Chemistry
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URN: urn:nbn:se:su:diva-232422DOI: 10.1038/s41467-024-48837-6ISI: 001234660500001PubMedID: 38806453Scopus ID: 2-s2.0-85194840603OAI: oai:DiVA.org:su-232422DiVA, id: diva2:1889318
Available from: 2024-08-15 Created: 2024-08-15 Last updated: 2024-08-15Bibliographically approved

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