The flexibility in the proline ring couples to the protein backbone

Authors

  • Bosco K. Ho,

    Corresponding author
    1. Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California 94148, USA
    • Department of Pharmaceutical Chemistry, University of California San Francisco, 600 16th Street, San Francisco, CA 94148, USA; fax: (415) 502-4222.
    Search for more papers by this author
  • Evangelos A. Coutsias,

    1. Department of Mathematics and Statistics, University of New Mexico, Albuquerque, New Mexico 87131, USA
    Search for more papers by this author
  • Chaok Seok,

    1. School of Chemistry, College of Natural Sciences, Seoul National University, Seoul 151-747, Republic of Korea
    Search for more papers by this author
  • Ken A. Dill

    1. Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California 94148, USA
    Search for more papers by this author

Abstract

In proteins, the proline ring exists predominantly in two discrete states. However, there is also a small but significant amount of flexibility in the proline ring of high-resolution protein structures. We have found that this side-chain flexibility is coupled to the backbone conformation. To study this coupling, we have developed a model that is simply based on geometric and steric factors and not on energetics. We show that the coupling between ϕ and χ1 torsions in the proline ring can be described by an analytic equation that was developed by Bricard in 1897, and we describe a computer algorithm that implements the equation. The model predicts the observed coupling very well. The strain in the Cγ-Cδ-N angle appears to be the principal barrier between the UP and DOWN pucker. This strain is relaxed to allow the proline ring to flatten in the rare PLANAR conformation.

Ancillary