Fischer-S; Dunbrack-RL; Karplus-M

JOURNAL-OF-THE-AMERICAN-CHEMICAL-SOCIETY. DEC 28 1994; 116 (26) :11931-11937, 1994.

The cis-trans imide isomerization reaction of the proline dipeptide is
analyzed. It is shown that the reaction path is complex and involves the
imide bond torsion angle omega, the pyramidalization of the imide
nitrogen, and the proline backbone torsion angle psi. A virtual dihedral
angle zeta is found to be better suited for describing the progress of the
reaction than omega. Adiabatic energy maps are calculated as a function of
these coordinates with the empirical CHARMM potential and at the
6-31G*//3-21G ab initio level. The gas phase 6-31G* activation barriers for
trans --> cis isomerization from the optimized ground state to the transition
state are 17.9 and 20.7 kcal/mol for the clockwise (syn) and anticlockwise
(anti) path, respectively. A strong dependence of the activation barrier
on psi is found; its value can change the barrier by as much as 12kcal/mol.
For psi similar to 0 degrees, the C-terninal NH group can
interact with either the lone pair of the imide nitrogen (syn) or the
imide carbonyl oxygen (anti); both interactions result in a lowering of
the barrier. This "autocatalytic" stabilization of the transition state
has implications for the mechanism of catalysis in rotamases.