Interaction of two peptide drugs with biomacromolecules analyzed by molecular docking and multi-spectroscopic methods

Peptide drugs, which are mainly used for the treatment of AIDS, myeloma, and breast cancer, have evolved rapidly owing to their high efficacy and low side effects. The interaction mechanisms of two peptide drugs with two biological macromolecules (protein and DNA), which are of great significance in disease prevention and drug design, were investigated using molecular docking, fluorescence spectroscopy, circular dichroism (CD) spectroscopy, UV-visible spectroscopy and viscosity measurements. The interaction between a series of common drugs and ovalbumin (OVA) was simulated by molecular docking, and two peptide drugs with the highest energy values, namely atazanavir and carfilzomib, were selected; the binding energy values of these drugs with OVA were -59.20 and -55.93 kcal/mol, respectively. The K_b values of the interaction of the two drugs with OVA/DNA were in the range of 10⁴-10⁷ M^-1, and the binding affinity of the drugs was stronger with OVA than with DNA. Hydrogen bonds and van der Waals forces were very important for the binding between drugs and OVA through molecular docking studies, and it was consistent with experimental results (ΔH < 0, ΔH < 0). The synchronous fluorescence spectrum showed that the interaction caused a change to the original structure of OVA, and atazanavir had a greater effect on OVA than carfilzomib. CD spectrum analysis also demonstrated that the conformation of OVA changed slightly. The interaction between atazanavir and DNA was mainly driven by hydrophobic forces (ΔH > 0 and ΔH > 0), whereas the major interaction forces involved in the binding of carfilzomib with DNA were hydrogen bonds and van der Waals forces. DNA melting studies, UV-visible spectroscopy, CD spectroscopy and viscosity measurements established that the interaction between the drugs and DNA was groove binding.