The winged-helix domain of the methyl methanesulfonate and ultraviolet sensitive 81 (wMUS81) is a potential cancer drug target. In this context, marine fungi compounds were indicated to be able to prevent wMUS81 structure. The work was established via molecular docking, molecular dynamics (MD), and replica exchange molecular dynamics (REMD) simulations. The binding free energy of ligands to wMUS81 was revealed using perturbation simulations. Eight compounds such as D197 (Tryptoquivaline U), D220 (Epiremisporine B), D67 (Aspergiolide A), D153 (Preussomerin G), D547 (12,13-dihydroxyfumitremorgin C), D152 (Preussomerin K), D20 (Marinopyrrole B), and D559 (Fumuquinazoline K) were indicated that they are able to prevent the conformation of wMUS81 via forming a strong binding affinity to the enzyme. The electrostatic interaction is the dominant factor in the binding process of ligands to wMUS81. The residues Trp55, Arg59, Leu62, His63, and Arg69 were found that they frequently form nonbonded contacts and hydrogen bonds to inhibitors. Moreover, the influence of the ligand D197, which formed the lowest binding free energy to wMUS81, on the structural change of enzyme was investigated using REMD simulations. The obtained results indicated that a ligand, which forms a strong binding affinity, can change the structure of wMUS81. Overall, the marine compounds probably inhibit wMUS81 due to forming a strong binding affinity to the enzyme as well as altering the enzymic conformation.

The molecular docking simulations were performed using AutoDock Vina

The MD simulations were performed using GROMACS 2019.4

The REMD simulations were performed using GROMACS 2019.4