Dynamics of Binding

So far, the studies of cucurbituril described have been thermodynamic investigations, in which factors contributing to the overall stability of molecular complexes have been explored. While bounteous, these only partly address the question of receptor specificity. For example, in biological systems the kinetics of noncovalent interactions, such as between enzymes and substrates, may be of greater consequence. Clearly, the dynamics of molecular recognition deserve additional attention. Cucurbituril provides diverse opportunities in this area [11]. 

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This reaction was followed by a second slower reaction that was not characterized in the report. An analysis of the overall results showed that the influence of steric or electrostatic effects on kinetic parameters is not necessarily minor. The dynamics of binding of NO to the diaqua species is mainly tuned by modulation of electron density on the iron center by the porphyrin macrocycle. A volume profile for NO binding based on values ofAV on and A V 0ff of + 1.5 and + 9.3 cm3/mol, respectively, maybe interpreted as an interchange mechanism for the on reaction, as the Fenl-H20 bond is decidedly stabilized (see Figure 7.15a). The volume of activation for the off reaction indicates a less dissociative mode of activation compared with NO release from other porphyrins. 

Van Aalten, D.M.F., Findlay, J.B.C., Amadei, A., Berendsen,H.J.C. Essential dynamics of the cellular retinol-binding protein. Evidence for ligand-induced conformational changes. Protein Engin. 8 (1995) 1129-1136. 

Hansson, T., Aqvist, J. Estimation of binding free energies for HIV proteinase inhibitors by molecular dynamics simulations. Prot. Eng. 8 (1995) 1137-1144... 

Guo Z and C L Brooks III 1998. Rapid Screening of Binding Affinities Application of the A-Dynamics Method to a Trypsin-Inhibitor System. Journal of the American Chemical Society 120 1920-1921. 

Hansson T and J Aqvist 1995. Estimation of Binding Free Energies for HIV Proteinase Inhibitors b Molecular Dynamics Simulations. Protein Engineering 8 1137-1144. 

One of the most important characteristics of micelles is their ability to take up all kinds of substances. Binding of these compounds to micelles is generally driven by hydrophobic and electrostatic interactions. The dynamics of solubilisation into micelles are similar to those observed for entrance and exit of individual surfactant molecules. Their uptake into micelles is close to diffusion controlled, whereas the residence time depends on the sttucture of the molecule and the solubilisate, and is usually in the order of 10 to 10" seconds . Hence, these processes are fast on the NMR time scale. 

DA Case, M Karplus. Dynamics of ligand binding to heme proteins. 1 Mol Biol 132 343-368, 1979. 

The binding and activation steps of receptor action have been dissected computationally, although not yet in a global fashion. The conformational dynamics of the activation of the A3AR have been approximated with respect to isolated portions of the receptor. 

The strict control of the activity of nuclear receptors by their respective ligands has recently permitted to follow the dynamics of DNA occupancy and to discover a surprising feature, which may be true also for other enhancer-binding factors. During transcriptional activation these transcription factors do not stably reside... 

We have already mentioned the application of supercomputers to biochemical simulations. Internal dynamics may play an Important role In such simulations. An example would be enzyme binding-site fluctuations that modulate reactivity or the dynamics of antigen-antibody association (11). In the specific case of diffusion-controlled processes, molecular recognition may occur because of long-range sterlc effects which are hard to assess without very expensive simulations (12.)-... 

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