Quantum mechanical calculation of the effects of stiff and rigid constraints in the conformational equilibrium of the alanine dipeptide.

If constraints are imposed on a macromolecule, two inequivalent classical models may be used: the stiff and the rigid one. This work studies the effects of such constraints on the conformational equilibrium distribution (CED) of the model dipeptide HCO-L-Ala-NH(2)without any simplifying assumption. We use ab initio quantum mechanics calculations including electron correlation at the MP2 level to describe the system, and we measure the conformational dependence of all the correcting terms to the naive CED based in the potential energy surface that appear when the constraints are considered. These terms are related to mass-metric tensors determinants and also occur in the Fixman's compensating potential. We show that some of the corrections are non-negligible if one is interested in the whole Ramachandran space. On the other hand, if only the energetically lower region, containing the principal secondary structure elements, is assumed to be relevant, then, all correcting terms may be neglected up to peptides of considerable length. This is the first time, as far as we know, that the analysis of the conformational dependence of these correcting terms is performed in a relevant biomolecule with a realistic potential energy function. (c) 2006 Wiley Periodicals, Inc. J Comput Chem, 2006.