Rare fluctuations of native proteins sampled by equilibrium hydrogen exchange.
We present a method for determining the ensembles of native protein structures that result from the large fluctuations of low probability revealed by hydrogen-exchange experiments. The measured protection factors are used to bias Monte Carlo simulations to sample the structures of the exchange competent species. The approach is illustrated by its application to the case of alpha-lactalbumin.
Vendruscolo
Michele
M
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
Paci
Emanuele
E
Dobson
Christopher M
CM
Karplus
Martin
M
D006801:Humans; D006859:Hydrogen / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D007700:Kinetics; D007768:Lactalbumin / Q000737:chemistry / Q000378:metabolism; D008956:Models, Chemical; D009010:Monte Carlo Method; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
D011506:Proteins; D006859:Hydrogen; D007768:Lactalbumin