<s>
GeNMR	B-Application
method	O
(	O
GEnerate	O
NMR	O
structures	O
)	O
is	O
the	O
first	O
fully	O
automated	O
template-based	O
method	O
of	O
protein	O
structure	O
determination	O
that	O
utilizes	O
both	O
NMR	O
chemical	O
shifts	O
and	O
NOE	O
-based	O
distance	O
restraints	O
.	O
</s>
<s>
In	O
addition	O
to	O
the	O
template-based	O
approach	O
,	O
the	O
GeNMR	B-Application
webserver	O
also	O
offers	O
an	O
ab	O
initio	O
protein	O
folding	O
mode	O
that	O
starts	O
folding	O
from	O
an	O
extended	O
structure	O
.	O
</s>
<s>
The	O
GeNMR	B-Application
web	O
server	O
produces	O
an	O
ensemble	O
of	O
PDB	O
coordinates	O
within	O
a	O
period	O
ranging	O
from	O
20	O
minutes	O
to	O
4	O
hours	O
,	O
depending	O
on	O
protein	O
size	O
,	O
server	O
load	O
,	O
quality	O
and	O
type	O
of	O
experimental	O
information	O
,	O
and	O
selected	O
protocol	O
options	O
.	O
</s>
<s>
GeNMR	B-Application
webserver	O
is	O
composed	O
of	O
two	O
parts	O
,	O
a	O
front-end	O
web-interface	O
(	O
written	O
in	O
Perl	O
and	O
HTML	O
)	O
and	O
a	O
back-end	O
consisting	O
of	O
eight	O
different	O
alignment	O
,	O
structure	O
generation	O
and	O
structure	O
optimization	O
programs	O
along	O
with	O
three	O
local	O
databases	O
.	O
</s>
<s>
GeNMR	B-Application
accepts	O
and	O
processes	O
backbone	O
and	O
side	O
chain	O
1H	O
,	O
13C	O
or	O
15N	O
chemical	O
shift	O
data	O
of	O
almost	O
any	O
combination	O
(	O
HA	O
only	O
,	O
HN	O
only	O
,	O
HA+HN	O
only	O
,	O
HA+HN+sidechain	O
H	O
,	O
CA	O
only	O
,	O
CA+CB	O
only	O
,	O
CA+CO	O
only	O
,	O
HA+CA+CB	O
,	O
HN+CA+CB	O
,	O
HN+15N	O
only	O
,	O
HN	O
,	O
+15N+CA	O
,	O
HN+15N+CA+CB	O
,	O
etc	O
.	O
)	O
.	O
</s>
<s>
This	O
allows	O
GeNMR	B-Application
to	O
handle	O
small	O
peptides	O
(	O
where	O
only	O
H	O
shifts	O
are	O
typically	O
measured	O
)	O
to	O
large	O
proteins	O
(	O
where	O
only	O
N	O
or	O
C	O
shifts	O
might	O
be	O
available	O
)	O
.	O
</s>
<s>
The	O
output	O
for	O
a	O
typical	O
GeNMR	B-Application
structure	O
calculation	O
consists	O
of	O
a	O
user-defined	O
set	O
of	O
lowest	O
energy	O
PDB	O
coordinates	O
in	O
a	O
simple	O
,	O
downloadable	O
text	O
format	O
.	O
</s>
<s>
A	O
flow	O
chart	O
describing	O
the	O
processing	O
logic	O
used	O
in	O
GeNMR	B-Application
is	O
shown	O
on	O
the	O
right	O
.	O
</s>
<s>
GeNMR	B-Application
makes	O
use	O
of	O
a	O
number	O
of	O
well-known	O
programs	O
and	O
databases	O
.	O
</s>
<s>
These	O
include	O
to	O
perform	O
structural	O
modeling	O
,	O
to	O
calculate	O
torsion	O
angles	O
from	O
chemical	O
shifts	O
,	O
for	O
comparative	O
modeling	O
and	O
alignment	O
and	O
CS23D	B-Application
to	O
calculate	O
protein	O
structures	O
from	O
chemical	O
shifts	O
only	O
.	O
</s>
<s>
GeNMR	B-Application
also	O
uses	O
several	O
well-known	O
external	O
programs	O
,	O
including	O
for	O
ab	O
initio	O
folding	O
without	O
NOEs	O
and	O
for	O
NOE-based	O
simulated	O
annealing	O
and	O
refinement	O
.	O
</s>
<s>
A	O
more	O
complete	O
list	O
of	O
GeNMR	B-Application
sub-programs	O
is	O
listed	O
on	O
the	O
CS23D	B-Application
page	O
.	O
</s>
<s>
GeNMR	B-Application
uses	O
homology	O
modeling	O
and	O
sequence/structure	O
threading	O
to	O
rapidly	O
generate	O
a	O
first-pass	O
model	O
of	O
the	O
query	O
protein	O
.	O
</s>
<s>
The	O
use	O
of	O
homology	O
modeling/threading	O
in	O
GeNMR	B-Application
allows	O
a	O
considerable	O
speed-up	O
in	O
its	O
structure	O
calculations	O
since	O
homology	O
models	O
can	O
often	O
be	O
generated	O
and	O
refined	O
in	O
a	O
minute	O
or	O
two	O
.	O
</s>
<s>
GeNMR	B-Application
also	O
makes	O
use	O
of	O
genetic	O
algorithms	O
to	O
allow	O
configurational	O
sampling	O
and	O
structural	O
refinement	O
using	O
non-differentiable	O
scores	O
,	O
such	O
as	O
ShiftX	O
chemical	O
shift	O
scores	O
.	O
</s>
<s>
GeNMR	B-Application
's	O
genetic	O
algorithm	O
creates	O
a	O
population	O
of	O
initial	O
structures	O
and	O
then	O
uses	O
combinations	O
of	O
mutations	O
,	O
cross-overs	O
,	O
segment	O
swaps	O
and	O
writhe	O
movements	O
to	O
comprehensively	O
sample	O
conformation	O
space	O
.	O
</s>
<s>
The	O
potential	O
functions	O
used	O
in	O
GeNMR	B-Application
are	O
derived	O
from	O
those	O
used	O
in	O
and	O
.	O
</s>
<s>
The	O
chemical	O
shift	O
component	O
of	O
the	O
GeNMR	B-Application
potential	O
uses	O
weighted	O
correlation	O
coefficients	O
calculated	O
between	O
the	O
observed	O
and	O
calculated	O
shifts	O
of	O
the	O
structure	O
being	O
refined	O
.	O
</s>
<s>
There	O
are	O
six	O
different	O
kinds	O
of	O
calculation	O
scenarios	O
that	O
GeNMR	B-Application
can	O
currently	O
accommodate	O
.	O
</s>
