Mixed anhydride reactivity by means of the molecular orbital AM1 and PM3 methods

Mechanism of action of aspartic proteinases: Application of transition-state analogue theory

“…The structures mimicking the complex of the catalytic center with a minimal substrate (Ac-FF-NHMe) (SUB), the tetrahedral intermediates (TIl and TI2), and the product (PROD) were adopted from our former work [26], in accordance with Fig. 2.…”

“…Using the formerly developed model of the catalytic center of aspartic proteinases [26], it was found that: (i) In a free enzyme the outer oxygen of Asp213 prefers to be protonated and that of Asp33 prefers to be dissociated within the catalytic COOH/COO-diad, in agreement with the finding of Iliadis et al [24]. (ii) In the Michaelis (SUB) and in the PROD complexes the reverse is true, while in the intermediate IT1 and IT2 complexes the Asp2r3 prefers to be protonated again, in agreement with the proposed mechanism [l l-131.…”

Computational Approaches to Biochemical Reactivity

“…Studies by Ciarkowski et al (1994) of the mechanism of AP by molecular mechanics with the MMX force field (Gajewski et al, 1990) and by semiempirical quantum mechanics methods AM1 and PM3 are hardly useful since energies are not reported for the first study while the model for a quantum mechanical study (constructed of two malonic acid molecules and water molecules that bridge the malonates) bears little resemblance to the X-ray structures of the active site of AP and includes effects that are not expected in the interaction of the peptide with the active site .…”