Interaction between β-lactoglobulin and EGCG under high-pressure by molecular dynamics simulation

The binding between {beta}-lactoglobulin and epigallocatechin gallate (EGCG) under the pressure of 600 MPa was explored using molecular docking and molecular dynamics (MD) simulation. EGCG bound mainly in two regions with site 1 in internal cavity of the {beta}-barrel and site 2 on the surface of protein. 150 ns MD was performed starting from the structure with the lowest binding energy at the two sites in molecular docking, respectively, it was found that the system fluctuated greatly when small molecule bound to site 2 at 0.1 MPa. The protein fluctuation and solvent accessible surface area became smaller under high-pressure. The binding of small molecules made the protein structure more stable with increasing of -helix and {beta}-sheet, while high-pressure destroyed -helix of protein. The binding free energy of small molecules at site 1was higher than that at site 2 under 0.1 MPa, with higher van der Waals and hydrophobic interaction at site 1 while more hydrogen bonds at site 2. The binding free energy of both sites decreased under high-pressure, especially at site 1, causing binding free energy at site 1 was lower than that at site 2 under high-pressure.