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 hyb rid quantum mechanical/molecular mechanical (QM/MM) procedure in the solvat ed enzyme. Apart from the pseudodiequatorial and pseudodiaxial conformers o f chorismate reported in the literature, new structures have been located u sing both methodologies. A comparative analysis of the results reveals the importance of the mechanical and electronic constraints imposed by the enzy me in this preequilibrium. These specific interactions between the substrat e and the enzyme environment change the order of stability of the different conformers obtained in vacuo, thus stabilizing those structures that can b e considered as the precursor for the rearrangement of chorismate to prephe nate. The deformation energy of the enzyme to mold the substrate into the a ctive site appears as the major factor in the energetic ordering of all the studied conformers.