Albany 2001

category image Biomolecular
SUNY at Albany
June 19-23, 2001

The Information Content of Single Molecule Experiments

Recent technological advances to micromanipulate single molecules with optical and magnetic "tweezers" have ushered a new way of doing biochemistry with single molecules (1). These techniques are increasingly being employed to study the single molecule dynamics of motor enzymes in the presence of externally applied forces.

Very interesting data have recently been obtained on the velocity of the DNA polymerase motor as a function of the force externally applied to the DNA template (2,3). We show how macroscopic and microscopic interpretations of single molecule data can lead to very different conclusions about the mechanism of this molecular motor. We emphasize the need to reconcile data from single molecule experiments with those from crystal structures.

Our theoretical analysis opens broader questions about the actual information content and insight into enzymatic mechanisms that can be reliably extracted from such single molecule experiments. With what theoretical tools and conceptual framework do we interpret single molecule data? And how can we integrate these data with previous bulk structural and kinetic studies on motor enzymes to build a consistent understanding of how these enzymes function?

References and Footnotes

  1. Mehta, A.D., Rief, Matthias, Spudich, J.A., Smith, D.A., Simmons, R.M., Single Molecule Biomechanics with Optical Methods. Science 283, 1689-1695 (1999).
  2. Wuite, G. J. L., Smith, S.B., Young, M., Keller, D., & Bustamante, C., Single-molecule studies of the effect of template tension on T7 DNA polymerase activity. Nature 404, 103-106 (2000).
  3. Maier, B., Bensimon, D., and Croquette, V.,Replication by a single DNA polymerase of a stretched single stranded DNA. Proc Natl Acad Sci, USA 97, 12002-12007 (2000).

Anita Goel

Department of Physics, & Harvard-MIT Joint Division of Health Harvard UniversitySciences and Technology (HST) Phone: 617-495-3328; Alt.Tel/Fax: 617-494-4721; email: goel@physics.harvard.edu