Molecular Dynamics Simulation and Free Energy Studies on the Interaction of Salicylic Acid with Human Serum Albumin (HSA)

Abstract

Human serum albumin (HSA) is the most abundant protein in the blood plasma. Molecular dynamics simulations of subdomain IIA of HSA and its complex with salicylic acid (SAL) were performed to investigate structural changes induced by the ligand binding. To estimate the binding affinity of SAL molecule to subdomains IB and IIA in HSA protein, binding free energies were calculated using the Molecular Mechanics-Generalized Born Surface Area (MM-GBSA). It is found that the presence of SAL molecule resulted in the stability of HSA. Also, ligand binding decreases the α-helix content of HSA. Binding free energy calculations demonstrate that the binding affinity of the SAL molecule to subdomain IIA of HSA is more than that of subdomain IB of HSA and the contributions of van der Waals interactions are more than that of electrostatics interactions. The per-residue decomposition of binding free energy suggested that the favorable residues with the most contribution in the binding free energy are hydrophobic, contributing to van der Waals interactions. Our important finding is that the subdomain IIA of HSA is the main HSA-SAL binding site. The results obtained are in good agreement with the corresponding experimental data.