Molecular interaction study of flavonols with human serum albumin by theoretical simulations

The human serum albumin (HSA)-drug binding characteristic is directly related to the pharmacokinetic, pharmacodynamic profile and side effect properties of drug. Though much is known about the protein binding characteristics of flavonol, the influence of molecular structure of flavonol and dynamic behaviour of protein conformations have received little attention. Here, we studied the interactions of HSA with flavonols by using molecular docking, molecular dynamics simulations coupled with molecular mechanics- Poisson Boltzmann/generalized Born surface area (MM-PB/GBSA) method. The results demonstrated the probable flavonol-binding position of HSA exist near the large hydrophobic cavity of Sudlow's site 1; and the predicted binding free energies of HSA-flavonol complexes were consistent with the trend of the experimental data that the binding affinity increased with the growth in number of hydroxyl groups on B-ring, and the van der Waals contribution is the dominated component for the binding; and Quercetin and Myricetin with one or two adjacent hydroxyl groups can exist stably in the binding pocket by strong hydrophobic interactions and extensive hydrogen bond interactions. The present work provides further information on the dynamical behaviors of binding pocket and reasonable binding models for HSA to five flavonols, and the adjacent hydroxyl groups introduced to B-ring might be beneficial to HSA-binding.