A flexible approach for understanding protein stability
- 6 October 2004
- journal article
- Published by Wiley in FEBS Letters
- Vol. 576 (3), 468-476
- https://doi.org/10.1016/j.febslet.2004.09.057
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
This publication has 50 references indexed in Scilit:
- Improved amino acid flexibility parametersProtein Science, 2003
- Origin of apparent fast and non-exponential kinetics of lysozyme folding measured in pulsed hydrogen exchange experimentsJournal of Molecular Biology, 2001
- Unfolding Kinetics of Tryptophan Side Chains in the Dimerization and Hinge Regions of HIV-I Protease Tethered Dimer by Real Time NMR SpectroscopyBiochemical and Biophysical Research Communications, 2000
- Contact order, transition state placement and the refolding rates of single domain proteins 1 1Edited by P. E. WrightJournal of Molecular Biology, 1998
- Folding and stability of a fibronectin type III domain of human tenascinJournal of Molecular Biology, 1997
- Structure-based Calculation of the Equilibrium Folding Pathway of Proteins. Correlation with Hydrogen Exchange Protection FactorsJournal of Molecular Biology, 1996
- Contribution of Hydrophobic Residues to the Stability of Human Lysozyme: Calorimetric Studies and X-ray Structural Analysis of the Five Isoleucine to Valine MutantsJournal of Molecular Biology, 1995
- Decomposition of the Free Energy of a System in Terms of Specific InteractionsJournal of Molecular Biology, 1994
- Normal mode refinement: Crystallographic refinement of protein dynamic structure: II. Application to human lysozymeJournal of Molecular Biology, 1992
- Structure of ubiquitin refined at 1.8 Å resolutionJournal of Molecular Biology, 1987