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A way to reduce the computational cost associated with the study of large molecules exploits the transfer of extremely localized molecular orbitals (ELMOs). Unfortunately, due to the reduction in the number of variational parameters, the ELMO description is not as accurate as the Hartree–Fock one, although it is qualitatively correct in most of the cases. Therefore, in order to overcome this significant drawback, we propose a perturbative ELMO approach exploiting the Hylleraas functional. Preliminary tests have been performed and the results are promising for future applications to large systems. [ABSTRACT FROM AUTHOR]

Protein farnesyltransferase (FTase) catalyzes farnesylation of a variety of peptide substrates. ³H α-secondary kinetic isotope effect (α-SKIE) measurements of two peptide substrates, CVIM and CVLS, are significantly different and have been proposed to reflect a rate-limiting SN2-like transition state with dissociative characteristics for CVIM, while, due to the absence of an isotope effect, CVLS was proposed to have a rate-limiting peptide conformational change. Potential of mean force quantum mechanical/molecular mechanical studies coupled with umbrella sampling techniques were performed to further probe this mechanistic dichotomy. We observe the experimentally proposed transition state (TS) for CVIM but find that CVLS has a symmetric SN2 TS, which is also consistent with the absence of a ±H α-SKIE. These calculations demonstrate facile substrate-dependent alterations in the transition state structure catalyzed by FTase. [ABSTRACT FROM AUTHOR]

Studies the catalytic mechanism of 5-aminoimidazole-4-carbozamide ribonucleiotide transformylase using pH dependent kinetics, site-directed mutagenesis and quantum chemical calculations. Proton shuttling processes; Lys residue determination; Activation energy of the reaction; Retention of the binding activity of the mutant enzyme for substrate.