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Atomistic simulation of carbohydrate-protein complex formation: Hevein-32 domain

Interactions between proteins and their small molecule ligands are of great importance for the process of drug design. Here we report an unbiased molecular dynamics simulation of systems containing hevein domain (HEV32) with N-acetylglucosamine mono-, di- or trisaccharide. Carbohydrate molecules wer...

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Detalles Bibliográficos
Autores principales: Solanke, Charles Oluremi, Trapl, Dalibor, Šućur, Zoran, Mareška, Václav, Tvaroška, Igor, Spiwok, Vojtěch
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6908686/
https://www.ncbi.nlm.nih.gov/pubmed/31831756
http://dx.doi.org/10.1038/s41598-019-53815-w
Descripción
Sumario:Interactions between proteins and their small molecule ligands are of great importance for the process of drug design. Here we report an unbiased molecular dynamics simulation of systems containing hevein domain (HEV32) with N-acetylglucosamine mono-, di- or trisaccharide. Carbohydrate molecules were placed outside the binding site. Three of six simulations (6 × 2 μs) led to binding of a carbohydrate ligand into the binding mode in agreement with the experimentally determined structure. Unbinding was observed in one simulation (monosaccharide). There were no remarkable intermediates of binding for mono and disaccharide. Trisaccharide binding was initiated by formation of carbohydrate-aromatic CH/π interactions. Our results indicate that binding of ligands followed the model of conformational selection because the conformation of the protein ready for ligand binding was observed before the binding. This study extends the concept of docking by dynamics on carbohydrate-protein interactions.