Characterization of the binding of angiotensin II receptor blockers to human serum albumin using docking and molecular dynamics simulation

Human serum albumin (HSA), the most abundant protein found in blood plasma, transports many drugs and ligands in the circulatory system. The drug binding ability of HSA strongly influences free drug concentrations in plasma, and is directly related to the effectiveness of clinical therapy. In current work, binding of HSA to angiotensin II receptor blockers (ARBs) are investigated using docking and molecular dynamics (MD) simulations. Docking results demonstrate that the main HSA–ARB binding site is subdomain IIIA of HSA. Simulation results reveal clearly how HSA binds with valsartan and telmisartan. Interestingly, electrostatic interactions appear to be more important than hydrophobic interactions in stabilizing binding of valsartan to HSA, and vice versa for HSA–telmisartan. The molecular distance between HSA Trp214 (donor) and the drug (acceptor) can be measured by fluorescence resonance energy transfer (FRET) in experimental studies. The average distances between Trp-214 and ARBs are estimated here based on our MD simulations, which could be valuable to future FRET studies. This work will be useful in the design of new ARB drugs with desired HSA binding affinity.