Browsing by Author "Banerjee, Kinshuk"

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    Accuracy of Substrate Selection by Enzymes Is Controlled by Kinetic Discrimination
    (American Chemical Society, 2017) Banerjee, Kinshuk; Kolomeisky, Anatoly B.; Igoshin, Oleg A.; Center for Theoretical Biological Physics
    Enzymes have the remarkable ability to select the correct substrate from the pool of chemically similar molecules. The accuracy of such a selection is determined by differences in the free-energy profiles for the right and wrong reaction pathways. Here, we investigate which features of the free-energy landscape govern the variation and minimization of selectivity error. It is generally believed that minimal error is affected by both kinetic (activation barrier heights) and thermodynamic (binding stability) factors. In contrast, using first-passage theoretical analysis, we show that the steady-state selectivity error is determined only by the differences in transition-state energies between the pathways and is independent of the energies of the stable complexes. The results are illustrated for two common catalytic mechanisms: (i) the Michaelis–Menten scheme and (ii) an error-correcting kinetic proofreading scheme with tRNA selection and DNA replication as guiding biological examples. Our theoretical analysis therefore suggests that the selectivity mechanisms are always kinetically controlled.