Abstract
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.
Highlights
Interactions between proteins and their small molecule ligands are of great importance for the process of drug design
The first binding site accommodates the non-reducing terminus. It is formed by residue Trp[23] together with two hydrogen-bonding residues (Tyr[30] binding to 3-OH of the saccharide by its hydroxyl group and Ser[19] binding to the carbonyl group of the acetyl moiety, by its hydroxyl group)
The residue Trp[21] forms the second binding site together with Glu[1], which interacts with NH bond of acetyl and simultaneously with 3-OH group
Summary
Interactions between proteins and their small molecule ligands are of great importance for the process of drug design. Trisaccharide binding was initiated by formation of carbohydrate-aromatic CH/π interactions. Understanding the nature of these interactions is necessary for the design of new molecules for therapeutic intervention of these processes. Carbohydrate-protein interactions are unique in many aspects, which makes them challenging to study by methods of molecular modeling and computational chemistry[2]. Multiple carbohydrate and protein molecules located on surfaces of cells interact much stronger than individual molecules. These interactions can be influenced more efficiently by multivalent carbohydrate molecules, such as carbohydrate-modified dendrimers, nanoparticles, surfaces and glyco-clusters. Several binding poses may have similar energy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
