Intramolecular interaction energies in model alanine and glycine tetrapeptides. Evaluation of anisotropy, polarization, and correlation effects. A parallel ab initio HF/MP2, DFT, and polarizable molecular mechanics study

An extension of the SIBFA polarizable molecular mechanics procedure to flexible oligopeptides is reported. The procedure is evaluated by computing the relative conformational energies, δEconf, of the alanine tetrapeptide in 10 representative conformations, which were originally derived by Beachy et al. (J Am Chem Soc 1997, 119, 5908) to benchmark molecular mechanics procedures with respect to ab initio computations. In the present study, a particular emphasis is on the separable nature of the components of the energy and the particular impact of the polarization energy component on δEconf. We perform comparisons with respect to single‐point HF, DFT, LMP2, and MP2 computations done at the SIBFA‐derived energy minima. Such comparisons are made first for the 10 conformers derived from ϕ/ψ torsional angle energy‐minimization (the rigid rotor approach), and, in a second step, after allowing additional relaxation of the Cα centered valence angles. In both series of energy‐minimization, the SIBFA δEconf compared best with the LMP2 results using the 6‐311G** basis set, the rms being 1.3 kcal/mol. In the absence of the polarization component, the rms is 3.5 kcal/mol. In both series of minimizations, the magnitudes of δEconf, computed as differences with respect to the most stable conformer taken as energy zero, decrease along the series: HF > DFT > LMP2 > SIBFA > MP2, indicative of increasing stabilization of the most highly folded conformers. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 823–834, 2004