Binding interaction of quinoline derivatives with lysozyme: Spectroscopic, computational and photocleavage studies

This study explored the molecular binding interactions of four quinoline-based derivatives—namely4-(4′-formylphenoxy)-2-(5″-cyanopyridin-2″ylamino) quinoline ( M ), 4-(2′,6′-dimethyl-4′-formylphenoxy)-2-(5″-cyanopyridin-2″ylamino) quinoline ( C ), 4-(4′-cyanophenoxy)-2-(5″-cyanopyridin-2″ylamino) quinoline ( G ), and 4-(2′,6′-dimethyl-4′-cyanophenoxy)-2-(5″-cyanopyridin-2″ylamino) quinoline ( J ), which function as highly potent non-nucleoside inhibitors of HIV-1 reverse transcriptase inhibitors, with lysozyme using spectroscopic and computational approaches. Spectroscopic analyses of lysozyme under conditions with the four compounds demonstrated complexation between lysozyme and the respective compounds. All four compounds exhibited measurable binding affinity toward lysozyme, as reflected by their corresponding binding constants (K b ) in the range of 10 3 -10 4 Lmol −1 , and the number of binding sites was examined to be 1, demonstrating that the compounds were determined to occupy a single binding site on lysozyme. CD spectra showed the conformational change of lysozyme. The interaction was further investigated using molecular docking and molecular dynamics (MD) simulations, and the observations demonstrated strong consistency with the experimental data. Moreover, the photocleavage of lysozyme induced by the compounds was examined to evaluate the ability of each compound to cleave proteins at specific sites. Lysozyme was successfully cleaved by C, G , and J , with the probable cleavage position located between Trp108 – Val109. However, lysozyme cleavage by M was not achieved under the same conditions. The protein photocleavage results clarified the binding sites of four compounds on lysozyme, in agreement with the findings from the computational investigations.