Molecular Docking approach on the effect of Site- Selective and Site-Specific Drugs on the Molecular Interactions of Human Serum Albumin (HSA) -Acridinedione dye complex

Molecular Docking (Mol.dock) of resorcinol based acridinedione dyes (ADR1 and ADR2) with a globular protein, Human Serum Albumin (HSA) were carried out. Docking studies reveal that ADR2 dye binding with HSA is energetically more stable and feasible than ADR1 dye. ADR1 dye predominantly resides in site I and III of HSA rather than binding site II wherein, ADR1 dye acts as hydrogen bonding (HB) acceptor through its carbonyl oxygen. On the contrary, ADR2 dye resides in all the binding sites of HSA such that the dye acts as the HB donor through the NH hydrogen atom and the carbonyl oxygen of the amino acid acts as the HB acceptor. The stability of dye-protein complex in the presence of several non-steroidal anti-inflammatory drugs (NSAIDs) was carried out by employing specific site selective drugs (Sudlow binding site drugs). The energetics and the bimolecular interactions of various drugs with ADR1-HSA and ADR2-HSA were generated to ascertain the influence of drug and its governance on the binding affinity of dye-protein complex. Sudlow site I binding drugs were effective in decreasing the energetics of ADR1 dye-HSA complex whereas site II binding drugs predominantly decreases the affinity of ADR2 dye with HSA. However, the dyes efficiently displaces the site specific drugs from their specific binding sites of HSA which was not observed in the case of drugs on the displacing ability over dyes situated in different domains of protein. Mol.dock studies are employed as an authentic, reliable and most effective tool to ascertain the binding stability of host–guest complex as well as to ascertain the most probable location of several competing ligands in various domains of HSA

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?

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