FEBS Letters
Volume 576, Issue 3 , Pages 468-476, 22 October 2004

A flexible approach for understanding protein stability

Edited by Robert B. Russell

  • D.R. Livesay

      Affiliations

    • Department of Chemistry, California State Polytechnic University, Pomona, 3801 W Temple Ave, Pomona, CA 91768, USA
    • These authors contributed equally to this work.
    • ,
  • S. Dallakyan

      Affiliations

    • Department of Physics and Astronomy, California State University, Northridge, 18111 Nordhoff Street, Northridge, CA 91330-8268, USA
    • These authors contributed equally to this work.
    • ,
  • G.G. Wood

      Affiliations

    • Department of Physics and Astronomy, California State University, Northridge, 18111 Nordhoff Street, Northridge, CA 91330-8268, USA
    • ,
  • D.J. Jacobs

      Affiliations

    • Department of Physics and Astronomy, California State University, Northridge, 18111 Nordhoff Street, Northridge, CA 91330-8268, USA
    • Corresponding Author InformationCorresponding author

Received 19 August 2004; accepted 20 September 2004. published online 07 October 2004.

Abstract 

A distance constraint model (DCM) is presented that identifies flexible regions within protein structure consistent with specified thermodynamic condition. The DCM is based on a rigorous free energy decomposition scheme representing structure as fluctuating constraint topologies. Entropy non-additivity is problematic for naive decompositions, limiting the success of heat capacity predictions. The DCM resolves non-additivity by summing over independent entropic components determined by an efficient network-rigidity algorithm. A minimal 3-parameter DCM is demonstrated to accurately reproduce experimental heat capacity curves. Free energy landscapes and quantitative stability-flexibility relationships are obtained in terms of global flexibility. Several connections to experiment are made.

Keywords:  Protein stability, Conformational flexibility, Heat capacity, Free energy decomposition, Transition state, Network rigidity

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PII: S0014-5793(04)01186-X

doi:10.1016/j.febslet.2004.09.057

FEBS Letters
Volume 576, Issue 3 , Pages 468-476, 22 October 2004

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