20.500.12556/DKUM-94367 Unveiling polyphenol-protein interactions a comprehensive computational analysis Our study investigates polyphenol-protein interactions, analyzing their structural diversity and dynamic behavior. Analysis of the entire Protein Data Bank reveals diverse polyphenolic structures, engaging in various noncovalent interactions with proteins. Interactions observed across crystal structures among diverse polyphenolic classes reveal similarities, underscoring consistent patterns across a spectrum of structural motifs. On the other hand, molecular dynamics (MD) simulations of polyphenol-protein complexes unveil dynamic binding patterns, highlighting the influx of water molecules into the binding site and underscoring limitations of static crystal structures. Water-mediated interactions emerge as crucial in polyphenol-protein binding, leading to variable binding patterns observed in MD simulations. Comparison of high- and low-resolution crystal structures as starting points for MD simulations demonstrates their robustness, exhibiting consistent dynamics regardless of the quality of the initial structural data. Additionally, the impact of glycosylation on polyphenol binding is explored, revealing its role in modulating interactions with proteins. In contrast to synthetic drugs, polyphenol binding seems to exhibit heightened flexibility, driven by dynamic water-mediated interactions, which may also facilitate their promiscuous binding. Comprehensive dynamic studies are, therefore essential to understand polyphenol-protein recognition mechanisms. Overall, our study provides novel insights into polyphenol-protein interactions, informing future research for harnessing polyphenolic therapeutic potential through rational drug design. polyphenols polyphenol-protein complexes molecular dynamics simulations noncovalent interactions water-mediated interactions glycosylation dynamic behavior polifenoli simulacija dinamike molekul nekovalentne interakcije true false true BioMed Central Angleški jezik Slovenski jezik https://jcheminf.biomedcentral.com/ © The Author(s) 2025 Članek v reviji 2025-08-14 10:42:49 2025-08-14 10:42:50 2026-01-27 03:23:16 0000-00-00 00:00:00 2025 0 0 21 str. Published: 10 April 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 2024-04-11 2025-03-25 2025-04-10 547 233496067 10.1186/s13321-025-00997-3 1758-2946 s13321-025-00997-3.pdf s13321-025-00997-3.pdf 1 D7B60C3CF9B0B0D59697AB28CBBB1A59 e4649fd66c6e78c23cf76567b10de788aa5f9225c1d35f002618a08aba4c57df 9fc533a5-fabe-11f0-9b4e-00155d00018d https://dk.um.si/Dokument.php?lang=slv&id=202574 https://link.springer.com/article/10.1186/s13321-025-00997-3 0 a5ef3160-fabe-11f0-9b4e-00155d00018d https://dk.um.si/Dokument.php?lang=slv&id=202575 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0