On the Economics of Binding Energies

  • William P. Jencks
Conference paper


There is a widespread impression that the best, most specific small molecules that make things happen in biological processes are the molecules that bind most strongly to a specific binding site on a macromolecule. Evolution will certainly favor molecules that bind strongly enough to their receptor site that a significant fraction of these sites are occupied, under conditions when it is desirable for some event that results from the binding to occur. However, many active molecules do not bind very strongly to their receptor site and inactive molecules often bind more strongly that active ones. One reason that very strong binding is uncommon is that it is usually just as important for a molecule to be able to dissociate from its binding site as for it to bind readily; very large equilibrium constants for association lead to unacceptably slow rate constants for dissociation even if binding is diffusion controlled. However, a more fundamental reason that the most effective small molecules do not bind very strongly arises from the economics of the utilization of binding energies through interaction energies — as is well known, but often forgotten.


Binding Energy Transition State Interaction Energy Strong Binding Conformation Change 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer-Verlag Berlin Heidelberg 1986

Authors and Affiliations

  • William P. Jencks
    • 1
  1. 1.Graduate Department of BiochemistryBrandeis UniversityWalthamUSA

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