Conference paper

Rational design of biomimetics with QM/MM Car-Parrinello simulations

A parallel study of the radical-copper enzyme Galactose Oxidase (GOase) and a low mol. wt. analog of the active site (Wang et. al. , Science 279, 537 (1998)) was performed with dynamical d. functional and mixed quantum-classical (QM/MM) calcns. This combined approach enables a direct comparison of the properties of biomimetic and natural system throughout the course of the catalytic reaction. In both cases, five essential forms of the catalytic cycle have been investigated: the resting state in its semi reduced (catalytically inactive) and in its oxidized (catalytically active) form Asemi and Aox, resp.; a protonated intermediate B; the transition state for the rate detg. hydrogen abstraction step C, and its product D. For A and B the electronic properties of the biomimetic compd. are qual. very similar to the ones of the natural target. However, in agreement with the exptl. obsd. difference in catalytic activity, the calcd. activation energy for the hydrogen abstraction step is distinctly lower for GOase (16 kcal/mol)than for the mimetic compd. (21 kcal/mol). The enzymic transition state is stabilized by a delocalization of the unpaired spin d. over the sulfur-modified equatorial tyrosine Tyr272, an effect that due to geometric reasons, is essentially absent in the biomimetic compd. Further differences between the mimic and its natural target concern the structure of the product of the abstraction step which is characterized by a weakly coordinated aldehyde complex for the latter and by a tightly bound linear complex for the former. [on SciFinder (R)]


    • LCBC-CONF-2000-002

    Record created on 2006-02-27, modified on 2016-08-08


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