A COMPUTATIONAL MOLECULAR DOCKING STUDY OF THE COUPLING BETWEEN POLYOLS AND BOVINE β-LACTOGLOBULIN

Beta-lactoglobulin (β-Lg) is the predominant protein found in whey, comprising 70% of its total proteins. It is widely used in formulations and has remarkable technological properties, including the ability of binding and carrying small molecules. Polyol sweeteners, such as xylitol, mannitol, sorbitol and erythritol, are capable of forming complexes with proteins, which can modify their relative sweetness in food formulations. To the best of our knowledge, there is a lack of studies that investigated the potential β-Lg binding sites for hydrophilic molecules such as polyols. Hence, this study aimed to gain a better understanding of the protein molecular site and interactions underlying β-Lg/polyol complexation. Computational docking was employed to obtain β-Lg/polyol complexes, using the AutoDock package tools. Firstly, the crystallographic structure of β-Lg (ID: 3NP0) was relaxed in aqueous solution at 298 K, using the GROMOS 53a6 force field and the SPC model of explicit water molecules, which involved successive energy minimizations with gradual removal of the motion restrictions initially imposed to avoid loss of structure and thermodynamic incongruities in the system. The geometry of the polyol sweeteners and their topological parameterization compatible with the GROMOS 53a6 force field were also built. Three putative binding sites were identified in β-Lg for xylitol, two for mannitol and sorbitol, and only one for erythritol. The region encompassing theTrp19, Gln59, Glu44, Glu158, Glu159 and Tyr20 aa residues stood out for all four polyols evaluated in terms of geometric fit, intermolecular interaction amounts, as well as distances and angles of hydrogen bond interactions identified in the complexes. Emphasis should be given to the Gln59 aa residue, which interacted through strong hydrogen bonds with xylitol (2.13 Å), mannitol (2.29, 2.62 and 2.74 Å), sorbitol (1.98 and 2.22 Å) and erythritol (2.66 Å). Molecular dynamics simulations of these complexes are ongoing and are expected to provide more information about the temporal stability of the identified intermolecular interactions, as well as possible conformational changes in β-Lg due to polyol complexation.