Chemistry Reference
In-Depth Information
Figure 12
Ribbon view of cytochrome c at four different positions along one of the
folding trajectories.
(2) subsequent formation of a molten globule conformation, the structural fea-
tures of which (lower right side of Figure 12) are in agreement with fluorescence
energy transfer experiments,
135
and (3) continued rearrangements prior to the
protein folding to its native conformation (lower left side Figure 12).
The SDEL algorithm has also been used to study the folding of more
complicated systems, such as the wild-type human Cu, Zn superoxide dismu-
tase (SOD) dimer. SOD is a 153-residue, homodimeric, antioxidant enzyme
that dismutates superoxide ion to hydrogen peroxide and oxygen.
136
It is an
eight-strand, flattened,
-barrel protein with one copper and one zinc ion per
monomer.
137
This protein is involved in the familial form of amyotrophic lat-
eral sclerosis (FALS).
A 1.8-
˚
resolution Apo-SOD crystal structure (PDB 1HL4
138
) was used to
generate SDEL trajectories of monomer folding and dimerization (Figure 13).
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Initial analysis of a pair of trajectories showed a small population of folded but
separated monomers. Interestingly, approximately 15-20% of each monomer's
intrasubunit native contacts form when the subunit centers of mass are within a
few angstroms of their equilibrium position, with the remaining native contacts
forming when the monomers are farther away.
b
Recent Advances and Challenges
These applications, albeit focused on peptides and proteins, demonstrate
the potential of the SDEL algorithm to study conformational dynamics of
