Abstract
The binding of ligands to proteins often occurs at rates that approach the diffusion-controlled limit1. For spherical molecules with negligible interactions apart from isotropic reactivity on contact, the diffusion-controlled rate constant is KD≡ 4πRD, where R is the distance between molecular centres at contact and D is the relative translational diffusion constant1–3. Deviations from this limiting rate due to interaction potentials4,5, hydrodynamic interactions6,7 and static geometric features of the binding sites8–13 have previously received much attention. Here, we point out another possible cause of such deviations, the dynamic modulation of binding site accessibility due to internal motions of the protein. Such motions may occur, for example, in proteins such as lysozyme, in which the active site cleft opens and closes in a stochastic manner14,15.
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McCammon, J., Northrup, S. Gated binding of ligands to proteins. Nature 293, 316–317 (1981). https://doi.org/10.1038/293316a0
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DOI: https://doi.org/10.1038/293316a0
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