Channeling by proximity: The catalytic advantages of active site colocalization using brownian dynamics

Patricia Bauler, Gary Huber, Thomas Leyh, J. Andrew McCammon

Research output: Contribution to journalArticlepeer-review

102 Scopus citations


Nature often colocalizes successive steps in a metabolic pathway. Such organization is predicted to increase the effective concentration of pathway intermediates near their recipient active sites and to enhance catalytic efficiency. Here, the pathway of a two-step reaction is modeled using a simple spherical approximation for the enzymes and substrate particles. Brownian dynamics are used to simulate the trajectory of a substrate particle as it diffuses between the active site zones of two different enzyme spheres. The results approximate distances for the most effective reaction pathways, indicating that the most effective reaction pathway is one in which the active sites are closely aligned. However, when the active sites are too close, the ability of the substrate to react with the first enzyme was hindered, suggesting that even the most efficient orientations can be improved for a system that is allowed to rotate or change orientation to optimize the likelihood of reaction at both sites.

Original languageEnglish (US)
Pages (from-to)1332-1335
Number of pages4
JournalJournal of Physical Chemistry Letters
Issue number9
StatePublished - May 6 2010


  • Biophysical Chemistry

ASJC Scopus subject areas

  • Materials Science(all)
  • Physical and Theoretical Chemistry


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