20.500.12556/DKUM-96180 Cheminformatic analysis of protein surfaces provides binding site insights andinforms identification strategies Aims: Understanding protein–ligand binding site behavior is central to structure-based drug design. Weanalyzed amino acid composition and interactions in protein–ligand small-molecule binding sites anddeveloped a novel method for binding site prediction.Materials and methods: We analyzed the PDBBind+ database, which contains the largest protein–ligand binding site dataset known to us, using existing cheminformatics packages and in-house code.We used the resulting data to train a binding site prediction model.Results: Within solvent-accessible binding regions, tryptophan, phenylalanine, tyrosine, methionine,and glycine, were enriched. Interaction analysis revealed hydrophobic contacts as the most frequent,followed by hydrogen bonds, water-bridged hydrogen bonds, salt bridges, π–π, π–cation, and occa-sional halogen interactions. We introduced the amino acid binding site enrichment index (ABSE), tosupport small-molecule binding site detection, and developed a model that discriminates binding sitesequences from protein surface patches with 0.91 accuracy.Conclusions: This work offers interpretable composition–interaction relationships and practical tool forbinding site characterization. To facilitate application, we provide a free, open-source, fast, bindingsiteidentification tool (AABS), available at https://gitlab.com/Jukic/aabs. We anticipate that these findingsand tool will advance binding site prediction and accelerate computationally intensive drug discoverywithin medicinal chemistry. protein surface analysis small-molecule binding site detection machine learning cheminformatics amino acidindex binding site mall-molecule–protein interactions in-silico drug design indeks aminokislin strojno učenje kemijska informatika proteini true false true Taylor&Francis Angleški jezik Slovenski jezik https://www.tandfonline.com/journals/ifmc20 © 2025 The Author(s). Članek v reviji 2025-12-08 12:39:05 2025-12-08 12:39:05 2026-05-16 03:14:27 0000-00-00 00:00:00 2025 0 0 str. 2945-2958 ǂVol. ǂ14 ǂissue ǂ24 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 2025-08-08 2025-11-06 2025-12-02 543 259712771 10.1080/17568919.2025.2592531 1756-8927 Cheminformatic_analysis_of_protein_surfaces_provides_binding_site_insights_and_informs_identification_strategies_(1).pdf Cheminformatic_analysis_of_protein_surfaces_provides_binding_site_insights_and_informs_identification_strategies_(1).pdf 1 8327D10A0650112C24E1B34BC8DB01F0 b0f25cda56823bcae512651c04270a4693eb33cfeac115b194e271ca31812476 91d95311-503c-11f1-9c27-00155d0001a1 https://dk.um.si/Dokument.php?lang=slv&id=206126 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0