Chemical models of enzymes

The terms mimicking enzymatic processes or chemical models of enzymes have no monosemantic and exact definitions. In some cases mimicking involves preceding a specific fast chemical reaction catalyzed by an enzyme in mild conditions. In other cases, attempts to construct chemical structures similar to an enzyme active site and to imitate different steps of an enzymatic process are made. Depending on the knowledge of the detailed structure and action mechanism of a target enzyme, starting positions of chemist are also diverse. 

Himo F (2006) Quantum chemical modeling of enzyme active sites and reaction mechanisms. TheorChem Acc 116 232-240... 

A key question in the action of enzymes is the understanding of the mechanisms by which they attain their catalytic rate enhancement relative to the uncatalyzed reactions. Some enzymes have been shown to produce rate accelerations as large as 1019 [1], The theoretical determination of the reaction mechanisms by which enzymes carry out the chemical reactions has been an area of great interests and intense development in recent years [2-11], A common approach for the modeling of enzyme systems is the QM/MM method proposed by Warshel and Levitt [12], In this method the enzyme is divided into two parts. One part includes the atoms or molecules that participate in the chemical process, which are treated by quantum mechanical calculations. The other contains the rest of the enzyme and the solvent, generally thousands of atoms, which is treated by molecular mechanics methods. 

A more realistic but still relatively simple model of enzyme catalysis includes binding of both substrate and product as described by Equation 11.9. This reaction is characterized by five individual rate constants k and k2, and k4 and k5, correspond to the forward and reverse binding steps of the substrate S and product P to the enzyme E, respectively, while k3 expresses the irreversible chemical conversion at the enzyme active site ... 

The topologically defined region(s) on an enzyme responsible for the binding of substrate(s), coenzymes, metal ions, and protons that directly participate in the chemical transformation catalyzed by an enzyme, ribo-zyme, or catalytic antibody. Active sites need not be part of the same protein subunit, and covalently bound intermediates may interact with several regions on different subunits of a multisubunit enzyme complex. See Lambda (A) Isomers of Metal Ion-Nucleotide Complexes Lock and Key Model of Enzyme Action Low-Barrier Hydrogen Bonds Role in Catalysis Yaga-Ozav /a Plot Yonetani-Theorell Plot Induced-Fit Model Allosteric Interaction... 

III. The Cluster Model Approach to Quantum Chemical Studies of Enzyme Reactions... 

Finally, an alternative to devising chemical models for enzymes is to make the enzymes themselves more attractive for large-scale synthesis by immobilization on insoluble supports.687 Immobilization of an enzyme would make a continuous process more practical and probably improve its stability, at the same time retaining the high selectivity and stereospecificity under mild conditions. 

Quantum chemical methods aim to treat the fundamental quantum mechanics of electronic structure, and so can be used to model chemical reactions. Such quantum chemical methods are more flexible and more generally applicable than molecular mechanics methods, and so are often preferable and can be easier to apply. The major problem with electronic structure calculations on enzymes is presented by the very large computational resources required, which significantly limits the size of the system that can be treated. To overcome this problem, small models of enzyme active sites can be studied in isolation (and perhaps with an approximate model of solvation). Alternatively, a quantum chemical treatment of the enzyme active site can be combined with a molecular mechanics description of the protein and solvent environment the QM/MM approach. Both will be described below. 

Shafirovich, V.Ya. (1995) Chemical models of reaction centers for photoinduced charge separation and photosynthetic enzyme systems, Ross. Khim. Zh. 39, 80-88. 

AIMD simulations appear as a promising tool for a first-principles modeling of enzymes. Indeed, they enable in situ simulations of chemical reactions furthermore, they are capable of tEiking crucial thermal effects [53] into account finally, they automatically include many of the physical effects so difficult to model in force-field based simulations, such as polarization effects, many-body forces, resonance stabilization of aromatic rings and hydration phenomena. 

The chemical modeling of active sites of enzymes can help to gain deeper insight into their catalytic mechanisms and might also lead to enzyme substitutes which are reliable and easy-to-handle tools for organic synthesis. Recently, it... 

As the concentration of the substrate increases, eventually a saturation point is reached beyond this point, the reaction cannot be further accelerated. The plot above is based on the model of enzyme catalysis expressed in the following chemical equation, where the enzyme (E) reacts with the substrate (S) to form some product or products (P). The rates of forward and reverse enzyme-substrate bonding are expressed as ki and k.i, and the rate of product molecule production is expressed as k2. 

IIIN) Selegny, E., Vincent, J. C. Model of Enzymic Temporal Chemical Oscillations in Homo-... 

The basis of the operational model is the experimental finding that the experimentally obtained relationship between agonist-induced response and agonist concentration resembles a model of enzyme function presented in 1913 by Louis Michaelis and Maude L. Menten. This model accounts for the fact that the kinetics of enzyme reactions differ significantly from the kinetics of conventional chemical reactions. It describes the reaction of a substrate with an enzyme as an equation of the form reaction velocity = (maximal velocity of the reaction x substrate concentration)/(concentration of substrate A a... 

There are two main models of enzyme action. In the lock-and-key model, when the key (substrate) fits the lock (active site), the chemical change begins. However, experiments show that, in many cases, the enzyme changes shape when the substrate lands at its active site. Thus, rather than a rigidly shaped lock in which a particular key fits, the induced-fit model pictures a hand (substrate) entering a glove (active site), causing it to attain its functional shape. 

Quantum Chemical Modeling of Enzymatic Reactions Applications to Epoxide-Transforming Enzymes... 

Therefore, the biomimetic approach, that is the aeation of chemical analogues of enzymes, seems to be especially promising in this respect. The aeation of chemical models of the enzymatic oxidation of alkanes and arenes makes it possible not only to understand its mechanisms better, but also to develop what are likely to be fundamentally new processes for the conversion of the hydrocarbon raw material. 

There is the increasing interest of investigators not only in the enzymatic oxidation of alkanes but also in the construction of chemical models of these reactions. The progress in the chemical simulation of enzymes demonstrates that novel efficient, highly selective catalytic systems for alkane oxidation will hopefully be created based on them in the future. 

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