Perkins &co-workers (Perkins et al. , 1994; Edwards &Perkins, 1995)
used an alignment of 92 sequences together
with spectroscopic data, and prediction algorithms to predict that
the vWf domain would comprise a repeating arrangement of strands
and
helices. Edwards &Perkins combined a THREADER scan with
analysis of the location of active site residues, a putative
disulphide bridge, and the principles of protein 3D structure.
They suggested that the vWf domain would be most likely to resemble ras p21.
The subsequently determined 3D structures
[Lee et al., 1995] showed this prediction of secondary structure and fold to
be largely correct [Russell \& Sternberg, 1995].
Our mapping technique allows many of the features
exploited by Perkins et al. to be combined in a prediction. Figure 2 shows a vWf
pattern based on the prediction of Perkins &co-workers
[Edwards \& Perkins, 1995][Perkins et al., 1994]. In addition to a pattern of predicted
secondary structures, the pattern also contains detailed information
as to the loop lengths, and details of two distance restraints: one
from a pair of aspartic acids thought to be involved in a metal
binding site (constrained to have their axial coordinates within 15
Å), and a putative disulphide bond (constrained to have their axial
coordinates within 9.5 Å). A tolerance of Å was added to
each of these restraints to allow for changes in secondary structure
packing across similar protein 3D structures.
A comparison of the vWf pattern to the database of 780 domains finds
Elongation factor Tu (PDB code 1ETU), Ras P21 (821P) and Che-Y (3CHY)
as the three top scoring folds, with other double-wound, ,
Rossmann-type folds following in the top 20 scoring folds. The top 3
scoring proteins are highly similar to the recently solved structures
of the vWf, with Ras P21/Elongation factor Tu being the most similar
[Lee et al., 1995].