Allostery without conformational change. A plausible model.
A general model is presented whereby ligand-induced changes in protein dynamics could produce allosteric communication between distinct binding sites, even in the absence of a macromolecular conformational change. Theoretical analysis, based on the statistical thermodynamics of ligand binding, shows that cooperative interaction free energies amounting to several kJ . mol-1 may be generated by this means. The effect arises out of the possible changes in frequencies and amplitudes of macromolecular thermal fluctuations in response to ligand attachment, and can involve all forms of dynamic behaviour, ranging from highly correlated, low-frequency normal mode vibrations to random local anharmonic motions of individual atoms or groups. Dynamic allostery of this form is primarily an entropy effect, and we derive approximate expressions which might allow the magnitude of the interaction in real systems to be calculated directly from experimental observations such as changes in normal mode frequencies and mean-square atomic displacements. Long-range influence of kinetic processes at different sites might also be mediated by a similar mechanism. We suggest that proteins and other biological macromolecules may have evolved to take functional advantage not only of mean conformational states but also of the inevitable thermal fluctuations about the mean.
D000494:Allosteric Regulation; D007700:Kinetics; D008954:Models, Biological; D011487:Protein Conformation; D011506:Proteins / Q000378:metabolism*; D013816:Thermodynamics
D011506:Proteins