Article,
Comparison of the transition state ensembles for folding of Im7 and Im9 determined using all-atom molecular dynamics simulations with phi value restraints
PROTEINS-STRUCTURE FUNCTION AND GENETICS, 54 (3): 513-525 (February 2004)
DOI: {10.1002/prot.10595}
Abstract
Delineation of the structural properties of transition states is key to
deriving models for protein folding. Here we describe the structures of
the transition states of the bacterial immunity proteins Im7 and Im9
obtained by all-atom molecular dynamics simulations with phi value
restraints derived from protein engineering experiments. This pair of
proteins is of special interest because, at pH 7 and 10 degreesC, Im7
folds via an intermediate while Im9 folds with a two-state transition.
The structures of the transition states for Im7 and Im9, together with
their radii of gyration and distances from the native state, are
similar. The typical distance between any two members of the transition
state ensemble of both proteins is large, with that of Im9 nearly twice
that of Im7. Thus, a broad range of structures make up the transition
state ensembles of these proteins. The ensembles satisfy the set of
rather low phi values and yet are consistent with high beta(T) values
(> 0.85 for both proteins). For both Im7 and Im9 the inter-helical
angles are highly variable in the transition state ensembles, although
the native contacts between helices I and IV are well conserved. By
measuring the distribution of the accessible surface area for each
residue we show that the hydrophobic residues that are buried in the
native state remain buried in the transition state, corresponding to a
hydrophobic collapse to a relatively ordered globule. The data provide
new insights into the structural properties of the transition states of
these proteins at an atomic level of detail and show that molecular
dynamics simulations with phi value restraints can significantly
enhance the knowledge of the transition state ensembles (TSE) provided
by the experimental phi values alone. (C) 2003 Wiley-Liss, Inc.
