Initial encounter complexes

The binary complex ES is commonly referred to as the ES complex, the initial encounter complex, or the Michaelis complex. As described above, formation of the ES complex represents a thermodynamic equilibrium, and is hence quantifiable in terms of an equilibrium dissociation constant, Kd, or in the specific case of an enzyme-substrate complex, Ks, which is defined as the ratio of reactant and product concentrations, and also by the ratio of the rate constants kM and km (see Appendix 2) ... 

As we have just seen, the initial encounter complex between an enzyme and its substrate is characterized by a reversible equilibrium between the binary complex and the free forms of enzyme and substrate. Hence the binary complex is stabilized through a variety of noncovalent interactions between the substrate and enzyme molecules. Likewise the majority of pharmacologically relevant enzyme inhibitors, which we will encounter in subsequent chapters, bind to their enzyme targets through a combination of noncovalent interactions. Some of the more important of these noncovalent forces for interactions between proteins (e.g., enzymes) and ligands (e.g., substrates, cofactors, and reversible inhibitors) include electrostatic interactions, hydrogen bonds, hydrophobic forces, and van der Waals forces (Copeland, 2000). 

For the enzyme isomerization mechanism illustrated in scheme C of Figure 6.3, there are two steps involved in formation of the final enzyme-inhibitor complex an initial encounter complex that forms under rapid equilibrium conditions and the slower subsequent isomerization of the enzyme leading to the high-affinity complex. The value of kohs for this mechanism is a saturable function of [/], conforming to the following equation ... 

It is evident that the initial encounter complex of DQS T is non-separable in a homogeneous aqueous phase and the photoproducts degrade in the cage structure. However, the SiC>2 colloid assists the separation of photoproducts from the cage structure (<(>s=0.26). 

Most of these theoretical investigations have been carried out using methyl compounds as the substrate. For example, the Sn2 reaction between OFT and methyl chloride has been investigated for non-linear and linear collisions using ab initio molecular dynamics calculations.105 The potential energy surface was calculated at the MP2/6-311-I— -G(2df,2pd) level of theory and the collision energy was set at 25 kcal mor1. The results for 495 trajectories indicated that the reactants pass from the initial encounter complex to the transition state in 0.02 ps and to the product encounter... 

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