Molecular docking approach on the binding stability of derivatives of phenolic acids (DPAs) with Human Serum Albumin (HSA): Hydrogen-bonding versus hydrophobic interactions or combined influences?

Abstract

Molecular docking (Mol.Doc) techniques were employed to ascertain the binding affinity and energetics of hydroxy derivatives of benzoic and cinnamic acids extract from Psidium guajava L. with Human Serum Albumin (HSA). Caffeic acid (CA), Ferullic acid (FA), Sinapic acid (SA), Syringic acid (SyA) and Vanillic acid (VA) are the derivatives phenolic acids (DPA) employed in docking studies which acts as the guest molecule. Docking of various feasible conformers of DPA with HSA (host) was explored and these conformers were categorized based on the docking score which is correlated to the binding energy (BE) and the stability depends upon the molecular interactions. Among the phenolic acids, SA-HSA complex was energetically more favorable and feasible based on BE and the order of binding stability upon complex formation of various DPA-HSA follows the order SA > FA = CA > VA > SyA, though SA and SyA are structurally similar to each other, likewise FA and VA exhibit a similar structure. The stability upon complex formation is correlated to the docking of the guest molecule in the binding domains of HSA and several molecular interactions. Hydrogen-bonding (HB) interaction governs the stability of host-guest complex is established. Interestingly, the presence of multiple hydrophobic interactions (pi-pi, pi-alkyl, pi-cation or anion, pi-sigma and pi-amide) competes over HB interaction in several conformers resulting in a decrease in BE. We report that SA acts as an excellent site selective and site-specific ligand that prefers to dock in Sudlow binding site II comprising of sub domains IIIA and IIIB respectively. However, all other phenolic acids do not behave neither as site selective nor site specific ligand such that they prefer to reside both in site II and site III (non-Sudlow binding site) of HSA. We authenticate that all the DPA as well as the amino acid moieties in HSA act as HB donor as well as acceptor sites apart from several hydrophobic interactions. We further establish that all the DPA has the least probable affinity to reside in binding site I (warfarin binding site), whereas sub domain IIIA of site II is the most preferred site which is energetically most favoured among all the sub domains.