Insights into the Interactions Between Bovine β‐Lactoglobulin and Reduced Coumarins: A Computational Perspective on Solubility Enhancement

Abstract The goal of this work is to investigate the role of bovine β‐lactoglobulin (ΒLG) in enhancing the solubility and bioavailability of reduced coumarins using in silico methods. Molecular docking and molecular dynamics (MD) simulations were explored to understand the interactions. Further, MM‐PBSA simulations were performed to get the change in free energy. The binding affinity from docking studies for 7‐ethyl‐4‐phenylchroman‐2‐one ( CMPD 226) with the 1GXA was found to be strongest and is −8.5 kcal/mol . RMSD and RMSF graphs were extracted from the MD simulations through GROMACS and AMBER and were compared. The MM‐PBSA study indicates a favourable binding interaction, with the change in enthalpy ( ΔH ) estimated at −28.04 kcal/mol. According to ADME studies, this molecule may improve the bioavailability and solubility of reduced coumarins. Key atomic movements using principal component analysis (PCA) of the complex were highlighted by eigenvector analysis, and flexible regions were identified as possible binding sites. The results of this study provide insightful information about the use of BLG in enhancing the solubility of CMPD226 significantly.