<s>
Phyre	B-Application
and	O
Phyre2	B-Application
(	O
Protein	O
Homology/AnalogY	O
Recognition	O
Engine	O
;	O
pronounced	O
as	O
'	O
fire	O
 '	O
)	O
are	O
free	O
web-based	O
services	O
for	O
protein	O
structure	O
prediction	O
.	O
</s>
<s>
Phyre	B-Application
is	O
among	O
the	O
most	O
popular	O
methods	O
for	O
protein	O
structure	O
prediction	O
having	O
been	O
cited	O
over	O
1500	O
times	O
.	O
</s>
<s>
Phyre2	B-Application
has	O
been	O
designed	O
to	O
ensure	O
a	O
user-friendly	O
interface	O
for	O
users	O
inexpert	O
in	O
protein	O
structure	O
prediction	O
methods	O
.	O
</s>
<s>
The	O
Phyre	B-Application
and	O
Phyre2	B-Application
servers	O
predict	O
the	O
three-dimensional	O
structure	O
of	O
a	O
protein	O
sequence	O
using	O
the	O
principles	O
and	O
techniques	O
of	O
homology	O
modeling	O
.	O
</s>
<s>
Because	O
the	O
structure	O
of	O
a	O
protein	O
is	O
more	O
conserved	O
in	O
evolution	O
than	O
its	O
amino	O
acid	O
sequence	O
,	O
a	O
protein	O
sequence	O
of	O
interest	O
(	O
the	O
target	O
)	O
can	O
be	O
modeled	O
with	O
reasonable	O
accuracy	O
on	O
a	O
very	O
distantly	O
related	O
sequence	O
of	O
known	O
structure	O
(	O
the	O
template	O
)	O
,	O
provided	O
that	O
the	O
relationship	O
between	O
target	O
and	O
template	O
can	O
be	O
discerned	O
through	O
sequence	B-Algorithm
alignment	I-Algorithm
.	O
</s>
<s>
The	O
first	O
Phyre	B-Application
server	O
was	O
released	O
in	O
June	O
2005	O
and	O
uses	O
a	O
profile-profile	O
alignment	O
algorithm	O
based	O
on	O
each	O
protein	O
's	O
position-specific	O
scoring	O
matrix	O
.	O
</s>
<s>
The	O
Phyre2	B-Application
server	O
was	O
publicly	O
released	O
February	O
2011	O
as	O
a	O
replacement	O
for	O
the	O
original	O
Phyre	B-Application
server	O
and	O
provides	O
extra	O
functionality	O
over	O
Phyre	B-Application
,	O
a	O
more	O
advanced	O
interface	O
,	O
fully	O
updated	O
fold	O
library	O
and	O
uses	O
the	O
HHpred	B-Application
/	I-Application
HHsearch	I-Application
package	O
for	O
homology	O
detection	O
among	O
other	O
improvements	O
.	O
</s>
<s>
After	O
pasting	O
a	O
protein	O
amino	O
acid	O
sequence	O
into	O
the	O
Phyre	B-Application
or	O
Phyre2	B-Application
submission	O
form	O
,	O
a	O
user	O
will	O
typically	O
wait	O
between	O
30	O
minutes	O
and	O
several	O
hours	O
(	O
depending	O
on	O
factors	O
such	O
as	O
sequence	O
length	O
,	O
number	O
of	O
homologous	O
sequences	O
and	O
frequency	O
and	O
length	O
of	O
insertions	O
and	O
deletions	O
)	O
for	O
a	O
prediction	O
to	O
complete	O
.	O
</s>
<s>
The	O
Phyre2	B-Application
results	O
screen	O
is	O
divided	O
into	O
three	O
main	O
sections	O
,	O
described	O
below	O
.	O
</s>
<s>
Phyre2	B-Application
provides	O
a	O
table	O
of	O
template	O
matches	O
color-coded	O
by	O
confidence	O
and	O
indicating	O
the	O
region	O
of	O
the	O
user	O
sequence	O
matched	O
.	O
</s>
<s>
The	O
main	O
results	O
table	O
in	O
Phyre2	B-Application
provides	O
confidence	O
estimates	O
,	O
images	O
and	O
links	O
to	O
the	O
three-dimensional	O
predicted	O
models	O
and	O
information	O
derived	O
from	O
either	O
Structural	O
Classification	O
of	O
Proteins	O
database	O
(	O
SCOP	O
)	O
or	O
the	O
Protein	O
Data	O
Bank	O
(	O
PDB	O
)	O
depending	O
on	O
the	O
source	O
of	O
the	O
detected	O
template	O
.	O
</s>
<s>
In	O
addition	O
Jmol	B-Language
is	O
used	O
to	O
permit	O
interactive	O
3D	O
viewing	O
of	O
the	O
protein	O
model	O
.	O
</s>
<s>
Phyre2	B-Application
uses	O
a	O
fold	O
library	O
that	O
is	O
updated	O
weekly	O
as	O
new	O
structures	O
are	O
solved	O
.	O
</s>
<s>
The	O
batch	O
processing	O
feature	O
permits	O
users	O
to	O
submit	O
more	O
than	O
one	O
sequence	O
to	O
Phyre2	B-Application
by	O
uploading	O
a	O
file	O
of	O
sequences	O
in	O
FASTA	O
format	O
.	O
</s>
<s>
Thus	O
,	O
batch	O
jobs	O
will	O
often	O
take	O
longer	O
than	O
individually	O
submitted	O
jobs	O
,	O
but	O
this	O
is	O
necessary	O
to	O
allow	O
a	O
fair	O
distribution	O
of	O
computing	O
resources	O
to	O
all	O
Phyre2	B-Application
users	O
.	O
</s>
<s>
This	O
may	O
be	O
for	O
example	O
a	O
newly	O
solved	O
structure	O
that	O
is	O
not	O
in	O
the	O
Phyre2	B-Application
database	O
or	O
because	O
of	O
some	O
additional	O
biological	O
information	O
that	O
indicates	O
the	O
chosen	O
template	O
would	O
produce	O
a	O
more	O
accurate	O
model	O
than	O
the	O
one(s )	O
automatically	O
chosen	O
by	O
Phyre2	B-Application
.	O
</s>
<s>
In	O
Phyre2	B-Application
an	O
uploaded	O
protein	O
structure	O
can	O
be	O
converted	O
into	O
a	O
hidden	O
Markov	O
model	O
and	O
then	O
scanned	O
against	O
a	O
set	O
of	O
genomes	O
(	O
more	O
than	O
20	O
genomes	O
as	O
of	O
March	O
2011	O
)	O
.	O
</s>
<s>
This	O
functionality	O
is	O
called	O
"	O
BackPhyre	O
"	O
to	O
indicate	O
how	O
Phyre2	B-Application
is	O
being	O
used	O
in	O
reverse	O
.	O
</s>
<s>
Sometimes	O
Phyre2	B-Application
ca	O
n't	O
detect	O
any	O
confident	O
matches	O
to	O
known	O
structures	O
.	O
</s>
<s>
If	O
a	O
confident	O
hit	O
is	O
detected	O
,	O
the	O
user	O
is	O
automatically	O
notified	O
by	O
email	O
together	O
with	O
the	O
results	O
of	O
the	O
Phyre2	B-Application
search	O
.	O
</s>
<s>
Phyre2	B-Application
is	O
coupled	O
to	O
the	O
3DLigandSite	O
server	O
for	O
protein	O
binding	O
site	O
prediction	O
.	O
</s>
<s>
Confident	O
models	O
produced	O
by	O
Phyre2	B-Application
(	O
confidence	O
>90	O
%	O
)	O
are	O
automatically	O
submitted	O
to	O
3DLigandSite	O
.	O
</s>
<s>
Phyre2	B-Application
permits	O
users	O
to	O
choose	O
'	O
Intensive	O
 '	O
modelling	O
from	O
the	O
main	O
submission	O
screen	O
.	O
</s>
<s>
The	O
complete	O
model	O
generated	O
by	O
Poing	O
is	O
combined	O
with	O
the	O
original	O
templates	O
as	O
input	O
to	O
MODELLER	B-Application
.	O
</s>
<s>
Applications	O
of	O
Phyre	B-Application
and	O
Phyre2	B-Application
include	O
protein	O
structure	O
prediction	O
,	O
function	O
prediction	O
,	O
domain	O
prediction	O
,	O
domain	O
boundary	O
prediction	O
,	O
evolutionary	O
classification	O
of	O
proteins	O
,	O
guiding	O
site-directed	O
mutagenesis	O
and	O
solving	O
protein	O
crystal	O
structures	O
by	O
molecular	O
replacement	O
.	O
</s>
<s>
There	O
are	O
two	O
linked	O
resources	O
that	O
use	O
Phyre	B-Application
predictions	O
for	O
the	O
structure-based	O
analysis	O
of	O
missense	O
variants	O
typically	O
resulting	O
from	O
single-nucleotide	O
polymorphisms	O
.	O
</s>
<s>
is	O
a	O
database	O
which	O
maps	O
genetic	O
variants	O
to	O
experimental	O
and	O
Phyre-predicted	O
protein	O
structures	O
.	O
</s>
<s>
Users	O
can	O
upload	O
their	O
own	O
variants	O
and	O
coordinates	O
,	O
including	O
both	O
PDB	O
structures	O
and	O
Phyre-predicted	O
models	O
.	O
</s>
<s>
Phyre	B-Application
and	O
Phyre2	B-Application
are	O
the	O
successors	O
to	O
the	O
3D-PSSM	O
protein	O
structure	O
prediction	O
system	O
which	O
has	O
over	O
1400	O
citations	O
to	O
date	O
.	O
</s>
<s>
Phyre	B-Application
and	O
Phyre2	B-Application
were	O
Lawrence	O
Kelley	O
in	O
the	O
Structural	O
bioinformatics	O
group	O
,	O
Imperial	O
College	O
London	O
.	O
</s>
<s>
Components	O
of	O
the	O
Phyre	B-Application
and	O
Phyre2	B-Application
systems	O
were	O
developed	O
by	O
Benjamin	O
Jefferys	O
,	O
Alex	O
Herbert	O
,	O
and	O
Riccardo	O
Bennett-Lovsey	O
.	O
</s>
