Network and graph analyses of folding free energy surfaces.
Protein folding is governed by a complex free energy surface whose entropic contributions are relevant because of the large number of degrees of freedom involved. Such complexity, in particular the conformational heterogeneity of the denatured state, is hidden in projections onto one or two order parameters (e.g. fraction of native contacts and/or radius of gyration), which usually results in relatively smooth surfaces. Recent approaches borrowed from network and graph theory have yielded quantitative unprojected representations of the free energy surfaces of a beta-hairpin and a three-stranded beta-sheet peptide using equilibrium folding-unfolding molecular dynamics simulations. Interestingly, the network and graph analyses of these structured peptides have revealed a very heterogeneous denatured state ensemble. It includes high-enthalpy, high-entropy conformations with fluctuating non-native secondary structure, as well as low-enthalpy, low-entropy traps.
Caflisch
Amedeo
A
Department of Biochemistry, University of Zurich, CH-8057 Zurich, Switzerland. caflisch@bioc.unizh.ch
D019295:Computational Biology; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D013499:Surface Properties