Probing of possible olanzapine binding site on human serum albumin: Combination of spectroscopic methods and molecular dynamics simulation

A Study on the Binding of Loperamide to Human Serum Albumin Using Combination of Computational and Experimental Methods

“…As discussed in literature [10,11], crystallographic data indicate that serum albumin, is a globular protein of 585 amino acids, comprises three homologous α-helical domains that are structurally similar: (denoted I, II, and III): domain I includes residues 1 to 195, domain II includes 196 to 383, and domain III includes 384 to 585; each domain has two subdomains (A and B) that assemble to form heart shaped molecule. The main sites of ligand binding of HSA are located in hydrophobic cavities in subdomains IIA and IIIA, which are corresponding to sites I and II, respectively.…”

“…During the 50 ns MD simulation was carried in the isobaric-isothermal ensemble (NPT: 300 K and 1 bar). Using the productive MD, pressure was kept constant at 1 bar by altering the box dimensions and the time-constant for pressure coupling was set to 1 Ps [10]. The topology parameters and topology file of protein were generated by using the Gromacs program (pdb2 gm x command).…”

“…This evidence denotes the change in solvent accessibility in the serum albumin resulted from interaction of LOP to a binding pocket in the vicinity of aromatic fluorophores particular Trp-214. The strong quenching of the serum albumin fluorescence proved the existence of interaction between LOP and serum albumin which changes the local environment around Trp-214 residue [10]. With the intention of determine the fluorescence quenching mechanism, the fluorescence quenching data at different temperatures (288, 298 and 308 K) ( Figure 4B-4D) were analysed using the classical Stern-Volmer equation (as discussed above).…”

“…Subsequently, the structures of HSA forming complexes with other compounds have been popular and extensively studied by other groups, such as our research group [10][11][12]. The well-characterized structure and folding of the HSA will help comprehend the interaction of LOP with serum albumin which in turn will shed light to biological functioning of LOP.…”

Comparative studies on drug binding to the purified and pharmaceutical-grade human serum albumins: Bridging between basic research and clinical applications of albumin

“…The binding of drugs to plasma proteins (especially albumin) affects their distribution and rate of metabolism [10]. Crystal structure analyses have revealed that HSA has two hydrophobic pockets as binding sites for aromatic and heterocyclic ligands; one site in subdomain IIA (commonly referred to as Sudlow's site I: warfarin-binding site) and the other within subdomain IIIA (commonly referred to as Sudlow's site II: indole/ benzodiazepine site) [11].…”