A Comprehensive Study on Theoretical and Experimental Effects of Nicotinic Acid and Picolinic Acid on the Structure and Stability of Human Serum Albumin

Abstract

The interaction of nicotinic acid (Nic) and picolinic acid (Pic), as two pyridine carboxylic acids, with human serum albumin (HSA) as a major transport protein in the blood was investigated using UV-Vis, fluorimetry, circular dichroism (CD), and molecular docking studies. The melting point (Tm) and ΔG0(298K) of HSA, as two thermodynamic parameters, were obtained from thermal denaturation of HSA with and without the presence of Nic and Pic. Tm values of 332.5, 336.4, and 333.9 K, and ΔG0(298K) of 97.4, 99.9, and 118.9 kJ/mol were recorded for HSA alone and following incubation with Nic and Pic, respectively. In chemical denaturation experiments utilizing guanidine hydrochloride (GuHCl), value of ΔG0H2O of 12.5, 16, and 15.3 kJ/mol, [Ligand]1/2 of 2.2, 2.4, and 2.3 M, and m of 5.6, 6.6, and 6.6 kJ/(mol × M) were recorded, respectively. The results of CD, UV-Vis spectroscopy, and molecular dynamics (MD) simulations showed that the binding of Nic and Pic to HSA induced conformational changes in HSA. Furthermore, the study of molecular docking indicated that the binding affinity of the Nic and Pic to site І (subdomain ІІA) is greater than that of site ІI (subdomain ІІIA) of HSA. These results provide valuable insights into the binding mechanisms of Nic and Pic to a plasma protein that is known to play an important role in the delivery of drugs to target organs.