Structure of the enzyme-substrate complex for guanosine triphosphate hydrolysis by elongation factor EF-Tu: Comparison of quantum mechanics/molecular mechanics and molecular dynamics results

The equilibrium geometric configurations of the enzyme-substrate complex for guanosine triphosphate hydrolysis by elongation factor EF-Tu calculated using two theoretical approaches, a combined quantum mechanics/molecular mechanics (QM/MM) method and a molecular dynamics method, are compared. The reaction complex geometry determined by the QM/MM method is consistent with the accepted reaction mechanism, whereas, in the enzyme-substrate structure predicted by the molecular dynamics method with the CHARMM force field, the relative positions of the nucleophilic reagent (water molecules) and the base (a histidine side chain) do not correspond to the optimal reagent arrangement.