<s>
Protein	B-Application
chemical	I-Application
shift	I-Application
re-referencing	I-Application
is	O
a	O
post-assignment	O
process	O
of	O
adjusting	O
the	O
assigned	O
NMR	O
chemical	O
shifts	O
to	O
match	O
IUPAC	O
and	O
BMRB	O
recommended	O
standards	O
in	O
protein	O
chemical	O
shift	O
referencing	O
.	O
</s>
<s>
The	O
first	O
program	O
to	O
comprehensively	O
tackle	O
chemical	O
shift	O
mis-referencing	O
in	O
biomolecular	O
NMR	O
was	O
SHIFTCOR	B-Application
.	O
</s>
<s>
SHIFTCOR	B-Application
is	O
an	O
automated	O
protein	O
chemical	O
shift	O
correction	O
program	O
that	O
uses	O
statistical	O
methods	O
to	O
compare	O
and	O
correct	O
predicted	O
NMR	O
chemical	O
shifts	O
(	O
derived	O
from	O
the	O
3D	O
structure	O
of	O
the	O
protein	O
)	O
relative	O
to	O
an	O
input	O
set	O
of	O
experimentally	O
measured	O
chemical	O
shifts	O
.	O
</s>
<s>
SHIFTCOR	B-Application
uses	O
several	O
simple	O
statistical	O
approaches	O
and	O
pre-determined	O
cut-off	O
values	O
to	O
identify	O
and	O
correct	O
potential	O
referencing	O
,	O
assignment	O
and	O
typographical	O
errors	O
.	O
</s>
<s>
SHIFTCOR	B-Application
identifies	O
potential	O
chemical	O
shift	O
referencing	O
problems	O
by	O
comparing	O
the	O
difference	O
between	O
the	O
average	O
value	O
of	O
each	O
set	O
of	O
observed	O
backbone	O
(	O
1Hα	O
,	O
13Cα	O
,	O
13Cβ	O
,	O
13CO	O
,	O
15N	O
and	O
1HN	O
)	O
shifts	O
and	O
their	O
corresponding	O
predicted	O
chemical	O
shifts	O
.	O
</s>
<s>
SHIFTCOR	B-Application
generates	O
and	O
reports	O
chemical	O
shift	O
offsets	O
or	O
differences	O
for	O
each	O
nucleus	O
.	O
</s>
<s>
The	O
results	O
contain	O
the	O
chemical	O
shift	O
analyses	O
(	O
including	O
lists	O
of	O
potential	O
mis-assignments	O
,	O
the	O
estimated	O
referencing	O
errors	O
,	O
the	O
estimated	O
error	O
in	O
the	O
calculated	O
reference	O
offset	O
(	O
95%	O
confidence	O
interval	O
)	O
,	O
the	O
applied	O
or	O
suggested	O
reference	O
offset	O
,	O
correlation	O
coefficients	O
,	O
RMSD	B-General_Concept
values	O
)	O
and	O
the	O
corrected	O
BMRB	O
formatted	O
chemical	O
shift	O
file	O
(	O
see	O
Figure	O
1	O
for	O
details	O
)	O
.	O
</s>
<s>
SHIFTCOR	B-Application
uses	O
the	O
chemical	O
shift	O
calculation	O
program	O
SHIFTX	O
to	O
predict	O
1Hα	O
,	O
13Cα	O
,	O
15N	O
shifts	O
based	O
on	O
the	O
3D	O
structure	O
coordinates	O
of	O
the	O
protein	O
being	O
analyzed	O
.	O
</s>
<s>
By	O
comparing	O
the	O
predicted	O
shifts	O
to	O
the	O
observed	O
shifts	O
,	O
SHIFTCOR	B-Application
is	O
able	O
to	O
accurately	O
identify	O
chemical	O
shift	O
reference	O
offsets	O
as	O
well	O
as	O
potential	O
mis-assignments	O
.	O
</s>
<s>
A	O
key	O
limitation	O
to	O
the	O
SHIFTCOR	B-Application
approach	O
is	O
that	O
requires	O
that	O
the	O
3D	O
structure	O
for	O
the	O
target	O
protein	O
be	O
available	O
to	O
assess	O
the	O
chemical	O
shift	O
reference	O
offsets	O
.	O
</s>
<s>
As	O
a	O
general	O
rule	O
,	O
PANAV	O
and	O
PSSI	O
typically	O
exhibit	O
a	O
smaller	O
spread	O
(	O
or	O
standard	B-General_Concept
deviation	I-General_Concept
)	O
in	O
calculated	O
reference	O
offsets	O
,	O
indicating	O
that	O
these	O
programs	O
are	O
slightly	O
more	O
precise	O
than	O
either	O
LACS	O
or	O
CheckShift	O
.	O
</s>
