Characterisation of transition state structures for protein folding using ‘high’, ‘medium’ and ‘low’ 
-values
1MRC Centre for Protein Engineering, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK 2Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK
3 To whom correspondence should be addressed. E-mail: mv245{at}cam.ac.uk (M.V.)/ jc162{at}cam.ac.uk (J.C.)
It has been suggested that 
-values, which allow structural information about transition states (TSs) for protein folding to be obtained, are most reliably interpreted when divided into three classes (high, medium and low). High -values indicate almost completely folded regions in the TS, intermediate -values regions with a detectable amount of structure and low -values indicate mostly unstructured regions. To explore the extent to which this classification can be used to characterise in detail the structure of TSs for protein folding, we used -values divided into these classes as restraints in molecular dynamics simulations. This type of procedure is related to that used in NMR spectroscopy to define the structure of native proteins from the measurement of inter-proton distances derived from nuclear Overhauser effects. We illustrate this approach by determining the TS ensembles of five proteins and by showing that the results are similar to those obtained by using as restraints the actual numerical -values measured experimentally. Our results indicate that the simultaneous consideration of a set of low-resolution -values can provide sufficient information for characterising the architecture of a TS for folding of a protein.
Keywords: CI2/-values/protein folding/restrained molecular dynamics simulations
Received December 18, 2007; accepted December 18, 2007.