Biomedical Engineering Reference
In-Depth Information
predictions of both w and y that are within 30u of reference values.
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The
NMR-based methods TALOS, TALOS+ and DANGLE all perform better
than this, achieving the same accuracy target in 75-86 % of cases and
confirming that chemical shift measurements do indeed convey useful
additional information.
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The original version of TALOS yields dihedral
angle values with low root mean square (RMS) errors (20-30u), but at the
expense of failing to make predictions at 28% of sites in query proteins; by
contrast, TALOS+ returns predictions for a larger proportion of sites (85%),
but at lower accuracy (Figure 3.6). DANGLE offers an acceptable compro-
mise, producing an RMS error rate close to that of TALOS while approaching
the degree of coverage observed for TALOS+ (Figure 3.6).
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The overall
accuracy of fragment-matching algorithms depends on the size and quality of
data in the reference database of chemical shifts and structures. The prospects
for improvement are therefore good, especially if information from NMR
solution
structures
can
be
incorporated
in
addition
to
that
from
high
resolution X-ray structures.
Besides w and y, it is also desirable to predict the backbone dihedral angle v.
Virtually all normal peptide bonds occur in the trans configuration, but 5.2% of
all Xaa-Pro peptide bonds adopt the cis configuration.
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A component of
PREDITOR
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and the specialised software tools POP
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and Promega
98
have
been devised to predict Xaa-Pro peptide bond conformations from proline
13
C9,
13
C
b
and
13
C
c
shift measurements. Other innovations concern the properties of
amino acid side-chains. With a focus on post-translational modifications,
random coil chemical shifts for phosphorylated serine, threonine and tyrosine
Figure 3.6
Scatter plots showing root mean square (RMS) errors against the degree
of completeness for various dihedral angle prediction methods, for (left) w
and (right) y. White data points indicate results from Real-SPINE 3.0;
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yellow: TALOS;
29
green: TALOS+;
31
blue: DANGLE.
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Results are for
all residue types in the 29 protein test set described in Cheung et al.
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