Force Field Modeling of Amino Acid Conformational Energies.

The conformational degrees of freedom for four amino acids in a model peptide environment have been sampled with density functional and second-order Møller-Plesset methods. Geometries have been optimized with an augmented double-ζ basis set and relative energies estimated by extrapolation of results using double, triple, and quadruple-ζ basis sets and including higher order correlation effects. In addition, the effects of vibrational zero point energies and solvation have been considered. The density functional method is unable to locate all the minima found at the MP2 level, which most likely is due to the inability for describing dispersion interactions. The use of basis sets smaller than augmented polarized double-ζ with the MP2 method may also in some cases lead to artifacts. The effects on relative energies by enlarging the basis set beyond an augmented triple-ζ and including higher order correlation beyond MP2 is small. The MP2/aug-cc-pVTZ level is recommended as a level of theory capable of an accuracy of ∼1 kJ/mol for relative conformational energies. Eight different force fields are tested for reproducing the electronic structure reference data. Force fields that represent the electrostatic energy by fixed partial charges typically only account for half of the conformations, while the AMOEBA force field, which includes multipole moments and polarizability, can reproduce ∼80% of the conformations in terms of geometry. This not only suggests that multipole moments and polarizability are important factors in designing new force fields but also indicates that there is still room for improvements.