<s>
SWISS-MODEL	B-Application
is	O
a	O
structural	O
bioinformatics	O
web-server	B-Application
dedicated	O
to	O
homology	O
modeling	O
of	O
3D	O
protein	O
structures	O
.	O
</s>
<s>
Today	O
,	O
SWISS-MODEL	B-Application
consists	O
of	O
three	O
tightly	O
integrated	O
components	O
:	O
(	O
1	O
)	O
The	O
SWISS-MODEL	B-Application
pipeline	O
–	O
a	O
suite	O
of	O
software	O
tools	O
and	O
databases	O
for	O
automated	O
protein	O
structure	O
modelling	O
,	O
(	O
2	O
)	O
The	O
SWISS-MODEL	B-Application
Workspace	O
–	O
a	O
web-based	O
graphical	O
user	O
workbench	O
,	O
(	O
3	O
)	O
The	O
SWISS-MODEL	B-Application
Repository	O
–	O
a	O
continuously	O
updated	O
database	O
of	O
homology	O
models	O
for	O
a	O
set	O
of	O
model	O
organism	O
proteomes	O
of	O
high	O
biomedical	O
interest	O
.	O
</s>
<s>
SWISS-MODEL	B-Application
pipeline	O
comprises	O
the	O
four	O
main	O
steps	O
that	O
are	O
involved	O
in	O
building	O
a	O
homology	O
model	O
of	O
a	O
given	O
protein	O
structure	O
:	O
</s>
<s>
BLAST	B-Application
and	O
HHblits	B-Application
are	O
used	O
to	O
identify	O
templates	O
.	O
</s>
<s>
The	O
templates	O
are	O
stored	O
in	O
the	O
SWISS-MODEL	B-Application
Template	O
Library	O
(	O
SMTL	O
)	O
,	O
which	O
is	O
derived	O
from	O
PDB	O
.	O
</s>
<s>
Alignment	B-Algorithm
of	O
target	O
sequence	O
and	O
template	O
structure(s )	O
.	O
</s>
<s>
SWISS-MODEL	B-Application
implements	O
a	O
rigid	O
fragment	O
assembly	O
approach	O
for	O
modelling	O
.	O
</s>
<s>
The	O
SWISS-MODEL	B-Application
Workspace	O
integrates	O
programs	O
and	O
databases	O
required	O
for	O
protein	O
structure	O
modelling	O
in	O
a	O
web-based	O
workspace	O
.	O
</s>
<s>
Depending	O
on	O
the	O
complexity	O
of	O
the	O
modelling	O
task	O
,	O
different	O
modes	O
of	O
usage	O
can	O
be	O
applied	O
,	O
in	O
which	O
the	O
user	O
has	O
different	O
levels	O
of	O
control	O
over	O
individual	O
modelling	O
steps	O
:	O
automated	O
mode	O
,	O
alignment	B-Algorithm
mode	O
,	O
and	O
project	O
mode	O
.	O
</s>
<s>
A	O
fully	O
automated	O
mode	O
is	O
used	O
when	O
a	O
sufficiently	O
high	O
sequence	B-Algorithm
identity	I-Algorithm
between	O
target	O
and	O
template	O
(	O
>50	O
%	O
)	O
allows	O
for	O
no	O
human	O
intervention	O
at	O
all	O
.	O
</s>
<s>
The	O
alignment	B-Algorithm
mode	O
enables	O
the	O
user	O
to	O
input	O
their	O
own	O
target-template	O
alignments	O
from	O
which	O
the	O
modelling	O
procedure	O
starts	O
(	O
i.e.	O
</s>
<s>
search	O
for	O
templates	O
step	O
is	O
skipped	O
and	O
rarely	O
only	O
minor	O
changes	O
in	O
the	O
provided	O
alignment	B-Algorithm
are	O
made	O
)	O
.	O
</s>
<s>
In	O
this	O
mode	O
the	O
input	O
is	O
a	O
project	O
file	O
that	O
can	O
be	O
generated	O
by	O
the	O
DeepView	O
(	O
Swiss	O
Pdb	O
Viewer	O
)	O
visualization	O
and	O
structural	O
analysis	O
tool	O
,	O
to	O
allow	O
the	O
user	O
to	O
examine	O
and	O
manipulate	O
the	O
target-template	O
alignment	B-Algorithm
in	O
its	O
structural	O
context	O
.	O
</s>
<s>
The	O
SWISS-MODEL	B-Application
Workspace	O
is	O
accessible	O
via	O
the	O
ExPASy	O
web	B-Application
server	I-Application
,	O
or	O
it	O
can	O
be	O
used	O
as	O
part	O
of	O
the	O
program	O
DeepView	O
(	O
Swiss	O
Pdb-Viewer	O
)	O
.	O
</s>
<s>
The	O
SWISS-MODEL	B-Application
Repository	O
provides	O
access	O
to	O
an	O
up-to-date	O
collection	O
of	O
annotated	O
three-dimensional	O
protein	O
models	O
for	O
a	O
set	O
of	O
model	O
organisms	O
of	O
high	O
general	O
interest	O
.	O
</s>
<s>
SWISS-MODEL	B-Application
Repository	O
is	O
integrated	O
with	O
several	O
external	O
resources	O
,	O
such	O
as	O
UniProt	O
,	O
InterPro	O
,	O
STRING	O
,	O
and	O
Nature	O
PSI	O
SBKB	O
.	O
</s>
<s>
New	O
developments	O
of	O
the	O
SWISS-MODEL	B-Application
expert	O
system	O
feature	O
(	O
1	O
)	O
automated	O
modelling	O
of	O
homo-oligomeric	O
assemblies	O
;	O
(	O
2	O
)	O
modelling	O
of	O
essential	O
metal	O
ions	O
and	O
biologically	O
relevant	O
ligands	O
in	O
protein	O
structures	O
;	O
(	O
3	O
)	O
local	O
(	O
per-residue	O
)	O
model	O
reliability	O
estimates	O
based	O
on	O
the	O
QMEAN	O
local	O
score	O
function	O
;	O
(	O
4	O
)	O
mapping	O
of	O
UniProt	O
features	O
to	O
models	O
.	O
</s>
<s>
(	O
1	O
)	O
and	O
(	O
2	O
)	O
are	O
available	O
when	O
using	O
the	O
automated	O
mode	O
of	O
the	O
SWISS-MODEL	B-Application
Workspace	O
;	O
(	O
3	O
)	O
is	O
always	O
provided	O
when	O
calculating	O
an	O
homology	O
model	O
using	O
the	O
SWISS-MODEL	B-Application
Workspace	O
,	O
and	O
(	O
4	O
)	O
is	O
available	O
in	O
the	O
SWISS-MODEL	B-Application
Repository	O
.	O
</s>
<s>
In	O
the	O
past	O
,	O
the	O
accuracy	O
,	O
stability	O
and	O
reliability	O
of	O
the	O
SWISS-MODEL	B-Application
server	O
pipeline	O
was	O
validated	O
by	O
the	O
EVA-CM	O
benchmark	O
project	O
.	O
</s>
<s>
Currently	O
,	O
the	O
SWISS-MODEL	B-Application
server	O
pipeline	O
is	O
participating	O
in	O
the	O
CAMEO3D	O
(	O
Continuous	O
Automated	O
Model	O
EvaluatiOn	O
)	O
project	O
which	O
continuously	O
evaluates	O
the	O
accuracy	O
and	O
reliability	O
of	O
protein	O
structure	O
prediction	O
services	O
in	O
a	O
fully	O
automated	O
manner	O
.	O
</s>
