A QM/MM study of the conformational equilibria in the chorismate mutase active site.: The role of the enzymatic deformation energy contribution

A conformational structures search of chorismate mutase substrate has been carried out using in vacuo AMI and MP2/6-31G* methods and by means of a hybrid quantum mechanical/molecular mechanical (QM/MM) procedure in the solvated enzyme. Apart from the pseudodiequatorial and pseudodiaxial conformers of chorismate reported in the literature, new structures have been located using both methodologies. A comparative analysis of the results reveals the importance of the mechanical and electronic constraints imposed by the enzyme in this preequilibrium. These specific interactions between the substrate and the enzyme environment change the order of stability of the different conformers obtained in vacuo, thus stabilizing those structures that can be considered as the precursor for the rearrangement of chorismate to prephenate. The deformation energy of the enzyme to mold the substrate into the active site appears as the major factor in the energetic ordering of all the studied conformers.