Multi-spectroscopic, thermodynamic, and molecular docking/dynamic approaches for characterization of the binding...

Studying the binding interaction between biological macromolecules and small molecules has formed the core of different research aspects. The interaction of palbociclib with calf thymus DNA at simulated physiological conditions (pH 7.4) was studied using different approaches, including spectrophotometry, spectrofluorimetry, FT-IR spectroscopy, viscosity measurements, ionic strength measurements, thermodynamic, molecular dynamic simulation, and docking studies. The obtained findings showed an apparent binding interaction between palbociclib and calf thymus DNA. Groove binding mode was confirmed from the findings of competitive binding studies with ethidium bromide or rhodamine B, UV-Vis spectrophotometry, and viscosity assessment. The binding constant (K_b) at 298 K calculated from the Benesi-Hildebrand equation was found to be 6.42 × 10³ M^-1. The enthalpy and entropy changes (∆H⁰ and ∆S⁰) were - 33.09 kJ mol^-1 and 61.78 J mol^-1 K^-1, respectively, showing that hydrophobic and hydrogen bonds constitute the primary binding forces. As indicated by the molecular docking results, palbociclib fits into the AT-rich region of the B-DNA minor groove with four base pairs long binding site. The dynamic performance and stability of the formed complex were also evaluated using molecular dynamic simulation studies. The in vitro study of the intermolecular binding interaction of palbociclib with calf thymus DNA could guide future clinical and pharmacological studies for the rational drug scheming with enhanced or more selective activity and greater efficacy.