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

C. O. Solanke1, D. Trapl1, Z. Šućur1, V. Mareška1, I. Tvaroška2 and V. Spiwok1

1Department of Biochemistry and Microbiology, University of Chemistry and Technology, Prague, Technická 3, Prague 6, 166 28, Czech Republic

2Institute of Chemistry – Centre for Glycomics, Slovak Academy of Sciences, Dúbravská cesta 9, Bratislava, 845 38, Slovakia

spiwokv@vscht.cz

Interactions between proteins and their small molecule ligands are of great importance for the process of drug design. Here we present our recent study, an unbiased molecular dynamics simulation of systems containing hevein domain (HEV32) with N-acetylglucosamine mono-, di- or trisaccharide [1]. Carbohydrate molecules were placed outside the binding site. Three of six simulations (each 2 μs) led to binding of a carbohydrate ligand into the binding mode in agreement with the experimentally determined structure. Unbinding and another binding 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. Results of essential dynamics also support the model of conformational selection. This study extends the concept of docking by dynamics on carbohydrate-protein interactions.

1. C. O. Solanke, D. Trapl, Z. Šućur, V. Mareška, I. Tvaroška , V. Spiwok,  Sci. Rep., 9, (2019), 18918.