Criteria complementarity

Therefore, complementarity between an asymmetric drug and its asymmetric receptor is often a criterion of drug activity. The effects of highly active or highly specific drugs depend more upon such complementarity than do those of weakly active drugs. Occasionally, the stereoselectivity of a drug is based on a specific and preferential metabolism of one isomer over the other, or on a biotransformation that selectively removes one isomer. Such... 

Although enzyme-transition state complementarity maximizes kcJKM, this is not a sufficient criterion for the maximization of the overall reaction rate. The reason is that the maximum reaction rate for a particular concentration of substrate depends on the individual values of cat and KM. It can be seen in Table 12.3, where some rates are calculated for various values of kcaX and KM (subject to kc.JKM being kept constant), that maximum rates are obtained for KM greater... 

Specificity between competing substrates depends on the relative binding of their transition states to the enzyme. Enzyme-transition state complementarity maximizes specificity because it ensures the optimal binding of the desired transition state. This is also the criterion for the optimal value of kcatIKM, which is not surprising, since specificity is determined by kcatIKM. Maximization of rate... 

The last criterion of the decision tree is the shape complementarity between the two interacting subunits within the cavity. The less favorable case is when both chains are densely packed and make many direct interactions within the cavity. As already mentioned, inhibitors should mimic the natural substrate but in addition they should make additional contacts that help enhance their potency. The cavity should therefore contain atoms that are not directly engaged in the interaction between the two proteins such that it is possible to design molecules that interact directly with them. Interfaces that possess... 

Although the structure of protein-protein complexes is not fully explained by geometric complementarity, this does appear to be a fairly common and relevant feature of macromolecular associations. The results presented support the assumption that surface shape complementarity, as evaluated by surface contact, can be a useful filtering criterion to reduce the number of possible alternative geometries to a manageable size, which may then be further evaluated. 

Thanks to their complementarity, metadynamics and replica exchange can nonetheless be optimally combined.To do so one has to perform simultaneous metadynamics simulations and adjust the Metropolis criterion to include the bias potential... 

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