Spectroscopic and computer science insights from the binding of palbociclib with bovine serum albumin

Spectroscopic and molecular simulation techniques are increasingly becoming powerful tools for studying the drug-protein binding acting. In this article, the conjugation features of palbociclib, a cell cycle-dependent kinase 4/6 (CDK4/6) inhibitor primarily used for HR+/HER2- breast cancer treatment, with bovine serum albumin (BSA) was examined in a physiomimetic setting. Based on the experimental results, the incorporation of a 1:1 palbociclib-BSA complex resulted in the intrinsic fluorescence quenching of BSA by palbociclib via static quenching. The results of competition experiments suggested that palbociclib has a higher probability for entering the BSA target Site III as compared to site I and site II. The thermodynamic and competition experiments yielded evidence to suggest that van der Waals forces, hydrogen bonding and hydrophobic interactions were responsible for the binding of palbociclib to BSA. Structural alterations resulting from palbociclib administration to BSA illustrated a minor influence of palbociclib on the advanced conformations of BSA. However, it led to an increase in hydrophobicity surrounding the tryptophan (Trp) and tyrosine (Tyr) residues. In addition, the experimental findings underwent a validation via the application of molecular docking and molecular dynamics simulations.