| Abstract
| - Cheminformatics is used to validate the capabilities of widely used quantum chemistry and molecularmechanics methods. Among the quantum methods examined are the semiempirical MNDO, AM1, and PM3methods, Hartree−Fock (ab initio) at a range of basis set levels, density functional theory (DFT) at a rangeof basis sets, and a post-Hartree−Fock method, local Møller−Plesset second-order perturbation theory(LMP2). Among the force fields compared are AMBER*, MMFF94, MMFF94s, OPLS/A, OPLS-AA, Sybyl,and Tripos. Programs used are Spartan, MacroModel, SYBYL, and Jaguar. The test molecule is (2-amino-5-thiazolyl)-alpha-(methoxyimino)-N-methylacetamide, a model of the aminothiazole methoxime (ATMO)side chain of third-generation cephalosporin antibacterial agents. The Ward hierarchical clustering techniqueyields an insightful comparison of experimental (X-ray) and calculated (energy optimized) bond lengthsand bond angles. The computational chemistry methods are also compared in terms of the potential energycurves they predict for internal rotation. Clustering analysis and regression analysis are compared. TheMMFF94 force field such as implemented in MacroModel is the best overall computational chemistry methodat reproducing crystallographic data and conformational properties of the ATMO moiety. This workdemonstrates that going to a higher level of quantum theory does not necessarily give better results and thatquantum mechanical results are not necessarily better than molecular mechanics results.
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