Study on effects of co-solvents on the structure of DhaA by molecular dynamics simulation

With the increasing application of enzymes in various research fields, the choices of co-solvents in enzymatic preparations which directly related to the catalytic activity have been attracted attention. Thus, researching on the stabilization or destabilization behaviors of enzymes in different solvents is extremely essential. In this study, the structural changes of DhaA in two typical aprotic co-solvents (acetonitrile and tetrahydrofuran) were firstly investigated by molecular dynamics (MD) simulation. The simulation results revealed the strong van der Waals force between co-solvents and DhaA which could induce the structural change of enzyme. Interestingly, the differences of molecular size and the electrostatic force with enzyme of two co-solvents led to quite different influences on DhaA. As for acetonitrile, solvent molecules could penetrate into the catalytic site of DhaA which promoted by the electrostatic interaction. On the contrary, tetrahydrofuran molecules were mainly distributed around the catalytic site due to the relative weak electrostatic interaction and steric resistance effect. It can be concluded that different co-solvent can affect the key domains, substrate pathway and catalytic pocket of DhaA.Communicated by Ramaswamy H. Sarma.