A molecular dynamics study on the binding of gemcitabine to human serum albumin

• HSA Sudlow sites (Ⅰ and Ⅱ) have a great capacity to adsorb considerable amounts of drugs. • GEM loading on these sites induced slight conformational changes in the HSA structure. • It also reduces the accumulated surface energy on these Sudlow sites. • The results show, H bonding is the main force of the stability of the GEM-HSA complex. • All observations also prove that the GEM on the Sudlow site Ⅱ has a higher stability. Human Serum Albumin (HSA) is introduced as one of the ideal protein-based nanoparticles for drug delivery due to some of its unique performances such as non-toxic, non-immunogenic, biocompatible, and biodegradable. Besides, the HSA has gained considerable attention owing to high compatibility without any severe side effects and extraordinary binding capacity of various drugs on its Sudlow sites (Ⅰ and Ⅱ). Hence, this study tries to explore and discuss the interactions between two Sudlow sites of HSA as the drug delivery agent and Gemcitabine (GEM), a drug used for treating cancerous tissues and cells, employing molecular dynamics. To investigate the adsorption phenomenon and the binding process of GEM on the Sudlow sites of HSA, the dynamics of GEM molecule, radial distribution function, radius of gyration, solvent-accessible surface area, hydrogen bonding, vdw energy, and free binding energy results are analyzed. The simulation results reveal that the binding of GEM molecules to the Sudlow sites of HSA induced slight conformational changes in the HSA structure. The results also illustrate that the GEM could strongly bind to the subdomain IIIA of HSA, and its stability on the site Ⅱ is higher than site Ⅰ. Hydrogen bonding as a non-bond interaction is the primary force in the stability of the GEM-HSA complex.