Correlated ab initio calculations have been carried out with a parallel version of the PSGVB electronic structure code to obtain relative energetics of a number of conformations of the alanine tetrapeptide. The highest level of theory utilized, local MP2 with the cc-pVTZ(−f) correlation-consistent basis set, has previously been shown to provide accurate 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 gas-phase tetrapeptide conformations and a β-sheet dipeptide dimer are compared with 20 different molecular mechanics force field parametrizations, providing the first assessment of the reliability of these models for systems larger than a dipeptide. Comparisons are made with the LMP2/cc-pVTZ(−f) results, which are taken as a benchmark for the tetrapeptides. Statistical summaries with regard to energetics and structure are produced for each force field, and a discussion of qualitative successes and failures is provided. The results display both the successes and limitations of the force fields studied and can be used as benchmark data in the development of new and improved force fields. In particular, comparisons of hydrogen-bonding energetics as a function of geometry suggest that future force fields will need to employ a representation for electrostatics that goes beyond the use of atom-centered partial charges.

Ab initio DFT quantum chemical methods are applied to study intermediates in the catalytic cycle of soluble methane monooxygenase hydroxylase (MMOH), a dinuclear iron-containing enzyme that converts methane and dioxygen selectively to methanol and water. The quantum chemical models reproduce reliably the X-ray crystallographic coordinates of the active site for the oxidized diiron(III) and reduced diiron(II) states to a high degree of structural precision. The results inspired a reexamination of the X-ray structure of reduced MMOH and revealed previously unassigned electron density now attributed to a key structural water molecule. The quantum chemical calculations required construction of a model containing about 100 atoms, which preserved key hydrogen bonding patterns necessary for structural integrity. Smaller models were unstable for the reduced form of the enzyme, an observation with significant mechanistic implications. The large model was then used to investigate the catalytic intermediates Hperoxo, formed upon the addition of dioxygen, and Q, the active species that reacts with methane. The structures, which differ significantly from alternatives proposed in the literature, are consistent with the experimentally available information concerning the spin states, geometries, and thermodynamics of formation of these intermediates. Other models that have been proposed, particularly in the case of Q, are ruled out in our calculations by energetic considerations, which have a simple physical interpretation. A bound water molecule is critical in assembling the catalytically active species Q.