Interaction of Heavy Metals with β-Lactoglobulin: Molecular Dynamics Study

Abstract

β-Lactoglobulin (β-lg), the predominant whey protein, is renowned for its nutritional and functional attributes, including its ability to bind hydrophobic and charged molecules. These properties make β-lg a promising candidate for applications such as drug delivery systems, nutraceutical carriers, and nanocomposites for environmental remediation, particularly in detecting and removing heavy metals. Despite its potential, the impact of heavy metal binding on β-lg's structure and stability remains insufficiently explored, posing challenges for its advanced applications. In this study, molecular dynamics (MD) simulations were employed to investigate the structural and dynamic responses of β-lg to the binding of heavy metal ions—Cd²⁺, Ni²⁺, Co³⁺, Pb²⁺, and Pt²⁺. A series of 200-ns MD simulations for the metal-protein complexes was conducted at 300 K using GROMACS software and the CHARMM General Force Field. Key structural parameters analyzed included backbone root-mean-square deviation (RMSD), radius of gyration (Rg), solvent-accessible surface area (SASA), and root-mean-square fluctuations (RMSF). The results demonstrated that binding of Cd²⁺, Ni²⁺, Co³⁺, Pb²⁺, and Pt²⁺ destabilized the protein's structure, with notable effects observed in critical regions such as the EF loop, H-strand, and AB loop. The extent of destabilization varied depending on the specific heavy metal ion. These findings emphasize the need for detailed residue-level analyses to fully elucidate the structural changes induced by metal binding and their implications for β-lg's functional properties. This work provides valuable insights into the behavior of β-lg under heavy metal binding and lays the groundwork for developing β-lg-based nanosystems for environmental and biomedical applications.