Characterizing the Binding Interaction between Erlotinib and Calf Thymus DNA In Vitro Using Multi‐Spectroscopic Methodologies and Viscosity Measurement Combined with Molecular Docking and DFT Calculation

Abstract

Abstract The binding interaction between erlotinib (ELTN) and calf thymus DNA (ct‐DNA) was characterized with the help of multi‐spectroscopic approaches, viscosity measurement and molecular docking as well as density functional theory (DFT) calculation to get critical information regarding ELTN binding to DNA. The findings confirmed that ELTN acted with ct‐DNA and formed the ELTN‐DNA complex with the binding constant of 2.37×10 3 M −1 (298 K) and the binding rate of ELTN was larger than 99% when C(ELTN)=8 μM and C(DNA) > 50.6 μM at 298 K, ELTN bound to the rich A−T minor groove of ct‐DNA, and the helical configuration of ct‐DNA slightly changes after binding ELTN but still kept B‐form while the conformation, atomic charge distribution, dipole moment, and frontier molecular orbitals of ELTN in the DNA complex obviously altered to satisfy with a larger global Hardness and the conformational adaptation. During the binding process, the ELTN interacting with ct‐DNA is endothermic, spontaneous, and entropy‐driven because of Δ H 0 > 0, Δ G 0 < 0, and |Δ H 0 |<|TΔ S 0 |, and the dominated driving force was hydrophobic interaction.