Enzyme reactions, quantum chemical investigations

Knowledge about the enzyme structure is usually a prerequisite to set up a quantum chemical model and investigate the reaction mechanism. However, there are cases where the energetic feasibility of reaction mechanisms can be evaluated by studying individual steps without information about the structures. One example is the study of pyruvate-form ate lyase (PFL), where the calculations were able to support one of the suggested mechanisms before the X-ray crystal structure was solved." Another example is the study of the reaction mechanism of spore-photoproduct lyase (SPL), for which the crystal structure still remains to be solved. ... 

The stereochemical requirements for optimal hydrogen-bond-catalysed enolization of carbonyl compounds by enzymes have been investigated by examination of crystallographic databases of relevant proteins and small molecules and by quantum chemical calculations on simple model reactions." Positioning hydrogen-bond donors perpendicular to the carbonyl plane induces strain in the catalyst-substrate complex, whereas the enolate appears to show negligible preference. 

Excited-states simulations were mainly limited to small and medium-sized molecules before the 90s. However, many important photophysical processes, as for example, the photoisomerization of rhodopsin, take place in a biological environment, seldom not without the presence of an enzyme. To study photochemical processes in the large-size systems, alternative methods are required. One such method, the QM/MM method," was developed by Warshel and Levitt in 1976. This approach combines the accuracy of quantum chemical models with the speed of molecular mechanics. An alternative method to combine different quantum chemical approaches, the ONIOM method, was developed by Morokuma and co-workers." These methods were initially used in the context of ground-state reactions. Early applications of the QM/MM hybrid method to photochemical processes can be found as early as 1982," however, it was not until at the beginning of this century that the method started to be used extensively for photochemical and photophysical dynamics. To find representative investigations of that time consult the reference list." " ... 

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