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Probe‐dependent and nonexponential relaxation kinetics: Unreliable signatures of downhill protein folding
Author(s) -
Hagen Stephen J.
Publication year - 2007
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21342
Subject(s) - kinetics , folding (dsp implementation) , relaxation (psychology) , protein folding , downhill folding , chemical physics , chemistry , energy landscape , energy (signal processing) , statistical physics , thermodynamics , physics , phi value analysis , classical mechanics , biology , biochemistry , neuroscience , electrical engineering , engineering , quantum mechanics
The theoretical suggestion that some proteins may encounter no significant free energy barriers during their folding raises an important question: What experimental signature does this downhill folding produce? Several authors have argued that nonexponential (and especially stretched exponential) or probe‐dependent kinetics represent useful experimental signatures of a downhill free energy surface. Here we examine more closely the connection between unusual kinetics and downhill energy surfaces. Simulation of diffusive relaxation dynamics on a variety of generically downhill, two‐dimensional free energy surfaces shows that these surfaces do not necessarily produce either probe‐dependent or significantly nonexponential kinetics. Conversely, we find that two‐dimensional surfaces with significant (>3 k B T ) energy barriers can readily give rise to nonexponential and probe‐dependent kinetics. These results show that downhill folding does not constitute a necessary or sufficient condition for nonexponential and/or probe‐dependent folding kinetics. One cannot easily prove or disprove that a protein folds downhill simply by studying its relaxation kinetics. Proteins 2007. © 2007 Wiley‐Liss, Inc.