Marine derivatives prevent w MUS81 in silico studies

The winged-helix domain of the methyl methanesulfonate and ultraviolet-sensitive 81 ( w MUS81) is a potential cancer drug target. In this context, marine fungi compounds were indicated to be able to prevent w MUS81 structure via atomistic 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 w MUS81 via forming a strong binding affinity to the enzyme via perturbation approach. The electrostatic interaction is the dominant factor in the binding process of ligands to w MUS81. The residues Trp55, Arg59, Leu62, His63 and Arg69 were found to frequently form non-bonded contacts and hydrogen bonds to inhibitors. Moreover, the influence of the ligand D197 , which formed the lowest binding free energy to w MUS81, on the structural change of enzyme was investigated using replica exchange molecular dynamics simulations. The obtained results indicated that D197 , which forms a strong binding affinity, can modify the structure of w MUS81. Overall, the marine compounds probably inhibit w MUS81 due to forming a strong binding affinity to the enzyme as well as altering the enzymic conformation.