ACCURATE AB-INITIO QUANTUM-CHEMICAL DETERMINATION OF THE RELATIVE ENERGETICS OF PEPTIDE CONFORMATIONS AND ASSESSMENT OF EMPIRICAL FORCE-FIELDS

Correlated ab initio calculations have been carried out with a paralle l version of the PSGVB electronic structure code to obtain relative en ergetics of a number of conformations of the alanine tetrapeptide. The highest level of theory utilized, local MP2 with the cc-pVTZ(-f) corr elation-consistent basis set, has previously been shown to provide acc urate conformational energies in comparison with experiment for a data set of small molecules. Comparisons with published and new canonical MP2 calculations on the alanine dipeptide are made. Results for ten ga s-phase tetrapeptide conformations and a beta-sheet dipeptide dimer ar e compared with 20 different molecular mechanics force field parametri zations, providing the first assessment of the reliability of these mo dels for systems larger than a dipeptide. Comparisons are made with th e LMP2/cc-pVTZ(-f) results, which are taken as a benchmark for the tet rapeptides. Statistical summaries with regard to energetics and struct ure are produced for each farce field, and a discussion of qualitative successes and failures is provided. The results display both the succ esses and limitations of the force fields studied and can be used as b enchmark data in the development of new and improved force fields. In particular, comparisons of hydrogen-bonding energetics as a function o f geometry suggest that future force fields will need to employ a repr esentation for electrostatics that goes beyond the use of atom-centere d partial charges.