<s>
Folding	B-Application
@home	I-Application
(	O
FAH	O
or	O
F	B-Application
@h	I-Application
)	O
is	O
a	O
distributed	B-Operating_System
computing	I-Operating_System
project	I-Operating_System
aimed	O
to	O
help	O
scientists	O
develop	O
new	O
therapeutics	O
for	O
a	O
variety	O
of	O
diseases	O
by	O
the	O
means	O
of	O
simulating	O
protein	O
dynamics	O
.	O
</s>
<s>
This	O
includes	O
the	O
process	O
of	O
protein	O
folding	O
and	O
the	O
movements	O
of	O
proteins	O
,	O
and	O
is	O
reliant	O
on	O
simulations	O
run	O
on	O
volunteers	O
 '	O
personal	B-Device
computers	I-Device
.	O
</s>
<s>
Folding	B-Application
@home	I-Application
is	O
currently	O
based	O
at	O
the	O
University	O
of	O
Pennsylvania	O
and	O
led	O
by	O
Greg	O
Bowman	O
,	O
a	O
former	O
student	O
of	O
Vijay	O
Pande	O
.	O
</s>
<s>
The	O
project	O
utilizes	O
graphics	B-Architecture
processing	I-Architecture
units	I-Architecture
(	O
GPUs	B-Architecture
)	O
,	O
central	B-General_Concept
processing	I-General_Concept
units	I-General_Concept
(	O
CPUs	B-Device
)	O
,	O
and	O
ARM	B-Architecture
processors	I-Architecture
like	O
those	O
on	O
the	O
Raspberry	B-Operating_System
Pi	I-Operating_System
for	O
distributed	B-Architecture
computing	I-Architecture
and	O
scientific	O
research	O
.	O
</s>
<s>
As	O
part	O
of	O
the	O
client	B-Operating_System
–	I-Operating_System
server	I-Operating_System
model	I-Operating_System
network	B-Architecture
architecture	I-Architecture
,	O
the	O
volunteered	O
machines	O
each	O
receive	O
pieces	O
of	O
a	O
simulation	O
(	O
work	O
units	O
)	O
,	O
complete	O
them	O
,	O
and	O
return	O
them	O
to	O
the	O
project	O
's	O
database	B-Application
servers	I-Application
,	O
where	O
the	O
units	O
are	O
compiled	O
into	O
an	O
overall	O
simulation	O
.	O
</s>
<s>
Volunteers	O
can	O
track	O
their	O
contributions	O
on	O
the	O
Folding	B-Application
@home	I-Application
website	O
,	O
which	O
makes	O
volunteers	O
 '	O
participation	O
competitive	O
and	O
encourages	O
long-term	O
involvement	O
.	O
</s>
<s>
Folding	B-Application
@home	I-Application
is	O
one	O
of	O
the	O
world	O
's	O
fastest	O
computing	O
systems	O
.	O
</s>
<s>
With	O
heightened	O
interest	O
in	O
the	O
project	O
as	O
a	O
result	O
of	O
the	O
COVID-19	O
pandemic	O
,	O
the	O
system	O
achieved	O
a	O
speed	O
of	O
approximately	O
1.22	O
exaflops	O
by	O
late	O
March	O
2020	O
and	O
reached	O
2.43	O
exaflops	O
by	O
April	O
12	O
,	O
2020	O
,	O
making	O
it	O
the	O
world	O
's	O
first	O
exaflop	B-General_Concept
computing	I-General_Concept
system	I-General_Concept
.	O
</s>
<s>
This	O
level	O
of	O
performance	O
from	O
its	O
large-scale	O
computing	O
network	O
has	O
allowed	O
researchers	O
to	O
run	O
computationally	B-General_Concept
costly	I-General_Concept
atomic-level	O
simulations	O
of	O
protein	O
folding	O
thousands	O
of	O
times	O
longer	O
than	O
formerly	O
achieved	O
.	O
</s>
<s>
Since	O
its	O
launch	O
on	O
October1	O
,	O
2000	O
,	O
Folding	B-Application
@home	I-Application
was	O
involved	O
in	O
the	O
production	O
of	O
226	O
scientific	O
research	O
papers	O
.	O
</s>
<s>
General-purpose	O
supercomputers	B-Architecture
have	O
been	O
used	O
to	O
simulate	O
protein	O
folding	O
,	O
but	O
such	O
systems	O
are	O
intrinsically	O
costly	O
and	O
typically	O
shared	O
among	O
many	O
research	O
groups	O
.	O
</s>
<s>
Further	O
,	O
because	O
the	O
computations	O
in	O
kinetic	O
models	O
occur	O
serially	O
,	O
strong	O
scaling	B-Architecture
of	O
traditional	O
molecular	O
simulations	O
to	O
these	O
architectures	O
is	O
exceptionally	O
difficult	O
.	O
</s>
<s>
Through	O
a	O
process	O
known	O
as	O
adaptive	O
sampling	O
,	O
these	O
conformations	O
are	O
used	O
by	O
Folding	B-Application
@home	I-Application
as	O
starting	O
points	O
for	O
a	O
set	O
of	O
simulation	O
trajectories	O
.	O
</s>
<s>
The	O
adaptive	O
sampling	O
Markov	O
state	O
model	O
method	O
significantly	O
increases	O
the	O
efficiency	O
of	O
simulation	O
as	O
it	O
avoids	O
computation	O
inside	O
the	O
local	O
energy	O
minimum	O
itself	O
,	O
and	O
is	O
amenable	O
to	O
distributed	B-Architecture
computing	I-Architecture
(	O
including	O
on	O
GPUGRID	B-Operating_System
)	O
as	O
it	O
allows	O
for	O
the	O
statistical	O
aggregation	O
of	O
short	O
,	O
independent	O
simulation	O
trajectories	O
.	O
</s>
<s>
In	O
other	O
words	O
,	O
it	O
achieves	O
linear	O
parallelization	B-Operating_System
,	O
leading	O
to	O
an	O
approximately	O
four	O
orders	B-Device
of	I-Device
magnitude	I-Device
reduction	O
in	O
overall	O
serial	O
calculation	O
time	O
.	O
</s>
<s>
Between	O
2000	O
and	O
2010	O
,	O
the	O
length	O
of	O
the	O
proteins	O
Folding	B-Application
@home	I-Application
has	O
studied	O
have	O
increased	O
by	O
a	O
factor	O
of	O
four	O
,	O
while	O
its	O
timescales	O
for	O
protein	O
folding	O
simulations	O
have	O
increased	O
by	O
six	O
orders	B-Device
of	I-Device
magnitude	I-Device
.	O
</s>
<s>
In	O
2002	O
,	O
Folding	B-Application
@home	I-Application
used	O
Markov	O
state	O
models	O
to	O
complete	O
approximately	O
a	O
million	O
CPU	B-Device
days	O
of	O
simulations	O
over	O
the	O
span	O
of	O
several	O
months	O
,	O
and	O
in	O
2011	O
,	O
MSMs	O
parallelized	B-Operating_System
another	O
simulation	O
that	O
required	O
an	O
aggregate	O
10million	O
CPU	B-Device
hours	O
of	O
computing	O
.	O
</s>
<s>
In	O
January	O
2010	O
,	O
Folding	B-Application
@home	I-Application
used	O
MSMs	O
to	O
simulate	O
the	O
dynamics	O
of	O
the	O
slow-folding	O
32-residue	O
NTL9	O
protein	O
out	O
to	O
1.52milliseconds	O
,	O
a	O
timescale	O
consistent	O
with	O
experimental	O
folding	O
rate	O
predictions	O
but	O
a	O
thousand	O
times	O
longer	O
than	O
formerly	O
achieved	O
.	O
</s>
<s>
The	O
model	O
consisted	O
of	O
many	O
individual	O
trajectories	O
,	O
each	O
two	O
orders	B-Device
of	I-Device
magnitude	I-Device
shorter	O
,	O
and	O
provided	O
an	O
unprecedented	O
level	O
of	O
detail	O
into	O
the	O
protein	O
's	O
energy	O
landscape	O
.	O
</s>
<s>
In	O
2010	O
,	O
Folding	B-Application
@home	I-Application
researcher	O
Gregory	O
Bowman	O
was	O
awarded	O
the	O
Thomas	O
Kuhn	O
Paradigm	O
Shift	O
Award	O
from	O
the	O
American	O
Chemical	O
Society	O
for	O
the	O
development	O
of	O
the	O
open-source	B-Application
MSMBuilder	O
software	O
and	O
for	O
attaining	O
quantitative	O
agreement	O
between	O
theory	O
and	O
experiment	O
.	O
</s>
<s>
The	O
goal	O
of	O
the	O
first	O
five	O
years	O
of	O
Folding	B-Application
@home	I-Application
was	O
to	O
make	O
advances	O
in	O
understanding	O
folding	O
,	O
while	O
the	O
current	O
goal	O
is	O
to	O
understand	O
misfolding	O
and	O
related	O
disease	O
,	O
especially	O
Alzheimer	O
's	O
.	O
</s>
<s>
The	O
simulations	O
run	O
on	O
Folding	B-Application
@home	I-Application
are	O
used	O
in	O
conjunction	O
with	O
laboratory	O
experiments	O
,	O
but	O
researchers	O
can	O
use	O
them	O
to	O
study	O
how	O
folding	O
in	O
vitro	O
differs	O
from	O
folding	O
in	O
native	O
cellular	O
environments	O
.	O
</s>
<s>
For	O
example	O
,	O
in	O
2011	O
,	O
Folding	B-Application
@home	I-Application
simulated	O
protein	O
folding	O
inside	O
a	O
ribosomal	O
exit	O
tunnel	O
,	O
to	O
help	O
scientists	O
better	O
understand	O
how	O
natural	O
confinement	O
and	O
crowding	O
might	O
influence	O
the	O
folding	O
process	O
.	O
</s>
<s>
In	O
2010	O
,	O
Folding	B-Application
@home	I-Application
used	O
GPUs	B-Architecture
to	O
simulate	O
the	O
unfolded	O
states	O
of	O
Protein	O
L	O
,	O
and	O
predicted	O
its	O
collapse	O
rate	O
in	O
strong	O
agreement	O
with	O
experimental	O
results	O
.	O
</s>
<s>
The	O
large	O
data	O
sets	O
from	O
the	O
project	O
are	O
freely	O
available	O
for	O
other	O
researchers	O
to	O
use	O
upon	O
request	O
and	O
some	O
can	O
be	O
accessed	O
from	O
the	O
Folding	B-Application
@home	I-Application
website	O
.	O
</s>
<s>
The	O
Pande	O
lab	O
has	O
collaborated	O
with	O
other	O
molecular	O
dynamics	O
systems	O
such	O
as	O
the	O
Blue	B-Operating_System
Gene	I-Operating_System
supercomputer	B-Architecture
,	O
and	O
they	O
share	O
home	O
's	O
key	O
software	O
with	O
other	O
researchers	O
,	O
so	O
that	O
the	O
algorithms	O
which	O
benefited	O
Folding	B-Application
@home	I-Application
may	O
aid	O
other	O
scientific	O
areas	O
.	O
</s>
<s>
In	O
2011	O
,	O
they	O
released	O
the	O
open-source	B-Application
Copernicus	O
software	O
,	O
which	O
is	O
based	O
on	O
home	O
's	O
MSM	O
and	O
other	O
parallelizing	O
methods	O
and	O
aims	O
to	O
improve	O
the	O
efficiency	O
and	O
scaling	B-Architecture
of	O
molecular	O
simulations	O
on	O
large	O
computer	B-Architecture
clusters	I-Architecture
or	O
supercomputers	B-Architecture
.	O
</s>
<s>
Summaries	O
of	O
all	O
scientific	O
findings	O
from	O
Folding	B-Application
@home	I-Application
are	O
posted	O
on	O
the	O
Folding	B-Application
@home	I-Application
website	O
after	O
publication	O
.	O
</s>
<s>
In	O
2008	O
,	O
Folding	B-Application
@home	I-Application
simulated	O
the	O
dynamics	O
of	O
Aβ	O
aggregation	O
in	O
atomic	O
detail	O
over	O
timescales	O
of	O
the	O
order	O
of	O
tens	O
of	O
seconds	O
.	O
</s>
<s>
Folding	B-Application
@home	I-Application
was	O
able	O
to	O
simulate	O
Aβ	O
folding	O
for	O
six	O
orders	B-Device
of	I-Device
magnitude	I-Device
longer	O
than	O
formerly	O
possible	O
.	O
</s>
<s>
In	O
December	O
2008	O
,	O
Folding	B-Application
@home	I-Application
found	O
several	O
small	O
drug	O
candidates	O
which	O
appear	O
to	O
inhibit	O
the	O
toxicity	O
of	O
Aβ	O
aggregates	O
.	O
</s>
<s>
In	O
2011	O
,	O
Folding	B-Application
@home	I-Application
completed	O
simulations	O
of	O
several	O
mutations	O
of	O
Aβ	O
that	O
appear	O
to	O
stabilize	O
the	O
aggregate	O
formation	O
,	O
which	O
could	O
aid	O
in	O
the	O
development	O
of	O
therapeutic	O
drug	O
therapies	O
for	O
the	O
disease	O
and	O
greatly	O
assist	O
with	O
experimental	O
nuclear	O
magnetic	O
resonance	O
spectroscopy	O
studies	O
of	O
Aβ	O
oligomers	O
.	O
</s>
<s>
Later	O
that	O
year	O
,	O
Folding	B-Application
@home	I-Application
began	O
simulations	O
of	O
various	O
Aβ	O
fragments	O
to	O
determine	O
how	O
various	O
natural	O
enzymes	O
affect	O
the	O
structure	O
and	O
folding	O
of	O
Aβ	O
.	O
</s>
<s>
Scientists	O
are	O
using	O
Folding	B-Application
@home	I-Application
to	O
study	O
the	O
structure	O
of	O
the	O
huntingtin	O
protein	O
aggregate	O
and	O
to	O
predict	O
how	O
it	O
forms	O
,	O
assisting	O
with	O
rational	O
drug	O
design	O
methods	O
to	O
stop	O
the	O
aggregate	O
formation	O
.	O
</s>
<s>
Folding	B-Application
@home	I-Application
has	O
simulated	O
this	O
and	O
other	O
fragments	O
to	O
clarify	O
their	O
roles	O
in	O
the	O
disease	O
.	O
</s>
<s>
In	O
2004	O
,	O
Folding	B-Application
@home	I-Application
was	O
used	O
to	O
perform	O
the	O
first	O
molecular	O
dynamics	O
study	O
of	O
the	O
refolding	O
of	O
p53	O
's	O
protein	O
dimer	O
in	O
an	O
all-atom	O
simulation	O
of	O
water	O
.	O
</s>
<s>
This	O
was	O
the	O
first	O
peer	O
reviewed	O
publication	O
on	O
cancer	O
from	O
a	O
distributed	B-Operating_System
computing	I-Operating_System
project	I-Operating_System
.	O
</s>
<s>
The	O
following	O
year	O
,	O
Folding	B-Application
@home	I-Application
powered	O
a	O
new	O
method	O
to	O
identify	O
the	O
amino	O
acids	O
crucial	O
for	O
the	O
stability	O
of	O
a	O
given	O
protein	O
,	O
which	O
was	O
then	O
used	O
to	O
study	O
mutations	O
of	O
p53	O
.	O
</s>
<s>
Folding	B-Application
@home	I-Application
is	O
also	O
used	O
to	O
study	O
protein	O
chaperones	O
,	O
heat	O
shock	O
proteins	O
which	O
play	O
essential	O
roles	O
in	O
cell	O
survival	O
by	O
assisting	O
with	O
the	O
folding	O
of	O
other	O
proteins	O
in	O
the	O
crowded	O
and	O
chemically	O
stressful	O
environment	O
within	O
a	O
cell	O
.	O
</s>
<s>
Using	O
Folding	B-Application
@home	I-Application
and	O
working	O
closely	O
with	O
the	O
Center	O
for	O
Protein	O
Folding	O
Machinery	O
,	O
the	O
Pande	O
lab	O
hopes	O
to	O
find	O
a	O
drug	O
which	O
inhibits	O
those	O
chaperones	O
involved	O
in	O
cancerous	O
cells	O
.	O
</s>
<s>
Researchers	O
are	O
also	O
using	O
Folding	B-Application
@home	I-Application
to	O
study	O
other	O
molecules	O
related	O
to	O
cancer	O
,	O
such	O
as	O
the	O
enzyme	O
Src	O
kinase	O
,	O
and	O
some	O
forms	O
of	O
the	O
engrailed	O
homeodomain	O
:	O
a	O
large	O
protein	O
which	O
may	O
be	O
involved	O
in	O
many	O
diseases	O
,	O
including	O
cancer	O
.	O
</s>
<s>
In	O
2011	O
,	O
Folding	B-Application
@home	I-Application
began	O
simulations	O
of	O
the	O
dynamics	O
of	O
the	O
small	O
knottin	O
protein	O
EETI	O
,	O
which	O
can	O
identify	O
carcinomas	O
in	O
imaging	O
scans	O
by	O
binding	O
to	O
surface	O
receptors	O
of	O
cancer	O
cells	O
.	O
</s>
<s>
In	O
2012	O
,	O
Folding	B-Application
@home	I-Application
assisted	O
with	O
the	O
discovery	O
of	O
a	O
mutant	O
form	O
of	O
IL-2	O
which	O
is	O
three	O
hundred	O
times	O
more	O
effective	O
in	O
its	O
immune	O
system	O
role	O
but	O
carries	O
fewer	O
side	O
effects	O
.	O
</s>
<s>
In	O
2005	O
,	O
Folding	B-Application
@home	I-Application
tested	O
a	O
new	O
quantum	O
mechanical	O
method	O
that	O
improved	O
upon	O
prior	O
simulation	O
methods	O
,	O
and	O
which	O
may	O
be	O
useful	O
for	O
future	O
computing	O
studies	O
of	O
collagen	O
.	O
</s>
<s>
Although	O
researchers	O
have	O
used	O
Folding	B-Application
@home	I-Application
to	O
study	O
collagen	O
folding	O
and	O
misfolding	O
,	O
the	O
interest	O
stands	O
as	O
a	O
pilot	O
project	O
compared	O
to	O
Alzheimer	O
's	O
and	O
Huntington	O
's	O
research	O
.	O
</s>
<s>
Folding	B-Application
@home	I-Application
is	O
assisting	O
in	O
research	O
towards	O
preventing	O
some	O
viruses	O
,	O
such	O
as	O
influenza	O
and	O
HIV	O
,	O
from	O
recognizing	O
and	O
entering	O
biological	O
cells	O
.	O
</s>
<s>
In	O
2011	O
,	O
Folding	B-Application
@home	I-Application
began	O
simulations	O
of	O
the	O
dynamics	O
of	O
the	O
enzyme	O
RNase	O
H	O
,	O
a	O
key	O
component	O
of	O
HIV	O
,	O
to	O
try	O
to	O
design	O
drugs	O
to	O
deactivate	O
it	O
.	O
</s>
<s>
Folding	B-Application
@home	I-Application
has	O
also	O
been	O
used	O
to	O
study	O
membrane	O
fusion	O
,	O
an	O
essential	O
event	O
for	O
viral	O
infection	O
and	O
a	O
wide	O
range	O
of	O
biological	O
functions	O
.	O
</s>
<s>
This	O
complexity	O
limits	O
typical	O
computer	O
simulations	O
to	O
about	O
ten	O
thousand	O
atoms	O
over	O
tens	O
of	O
nanoseconds	O
:	O
a	O
difference	O
of	O
several	O
orders	B-Device
of	I-Device
magnitude	I-Device
.	O
</s>
<s>
In	O
2006	O
,	O
scientists	O
applied	O
Markov	O
state	O
models	O
and	O
the	O
Folding	B-Application
@home	I-Application
network	O
to	O
discover	O
two	O
pathways	O
for	O
fusion	O
and	O
gain	O
other	O
mechanistic	O
insights	O
.	O
</s>
<s>
Following	O
detailed	O
simulations	O
from	O
Folding	B-Application
@home	I-Application
of	O
small	O
cells	O
known	O
as	O
vesicles	O
,	O
in	O
2007	O
,	O
the	O
Pande	O
lab	O
introduced	O
a	O
new	O
computing	O
method	O
to	O
measure	O
the	O
topology	B-Architecture
of	O
its	O
structural	O
changes	O
during	O
fusion	O
.	O
</s>
<s>
In	O
2009	O
,	O
researchers	O
used	O
Folding	B-Application
@home	I-Application
to	O
study	O
mutations	O
of	O
influenza	O
hemagglutinin	O
,	O
a	O
protein	O
that	O
attaches	O
a	O
virus	O
to	O
its	O
host	O
cell	O
and	O
assists	O
with	O
viral	O
entry	O
.	O
</s>
<s>
As	O
of	O
2012	O
,	O
Folding	B-Application
@home	I-Application
continues	O
to	O
simulate	O
the	O
folding	O
and	O
interactions	O
of	O
hemagglutinin	O
,	O
complementing	O
experimental	O
studies	O
at	O
the	O
University	O
of	O
Virginia	O
.	O
</s>
<s>
In	O
March	O
2020	O
,	O
Folding	B-Application
@home	I-Application
launched	O
a	O
program	B-Application
to	O
assist	O
researchers	O
around	O
the	O
world	O
who	O
are	O
working	O
on	O
finding	O
a	O
cure	O
and	O
learning	O
more	O
about	O
the	O
coronavirus	O
pandemic	O
.	O
</s>
<s>
Due	O
to	O
limits	O
in	O
computing	O
power	O
,	O
current	O
in	O
silico	O
methods	O
usually	O
must	O
trade	O
speed	O
for	O
accuracy	O
;	O
e.g.	O
,	O
use	O
rapid	O
protein	O
docking	O
methods	O
instead	O
of	O
computationally	B-General_Concept
costly	I-General_Concept
free	O
energy	O
calculations	O
.	O
</s>
<s>
In	O
2010	O
,	O
Folding	B-Application
@home	I-Application
used	O
MSMs	O
and	O
free	O
energy	O
calculations	O
to	O
predict	O
the	O
native	O
state	O
of	O
the	O
villin	O
protein	O
to	O
within	O
1.8	O
angstrom	O
( Å	O
)	O
root	B-General_Concept
mean	I-General_Concept
square	I-General_Concept
deviation	I-General_Concept
(	O
RMSD	B-General_Concept
)	O
from	O
the	O
crystalline	O
structure	O
experimentally	O
determined	O
through	O
X-ray	O
crystallography	O
.	O
</s>
<s>
Scientists	O
have	O
used	O
Folding	B-Application
@home	I-Application
to	O
research	O
drug	O
resistance	O
by	O
studying	O
vancomycin	O
,	O
an	O
antibiotic	O
drug	O
of	O
last	O
resort	O
,	O
and	O
beta-lactamase	O
,	O
a	O
protein	O
that	O
can	O
break	O
down	O
antibiotics	O
like	O
penicillin	O
.	O
</s>
<s>
These	O
sites	O
are	O
attractive	O
drug	O
targets	O
,	O
but	O
locating	O
them	O
is	O
very	O
computationally	B-General_Concept
costly	I-General_Concept
.	O
</s>
<s>
In	O
2012	O
,	O
Folding	B-Application
@home	I-Application
and	O
MSMs	O
were	O
used	O
to	O
identify	O
allosteric	O
sites	O
in	O
three	O
medically	O
relevant	O
proteins	O
:	O
beta-lactamase	O
,	O
interleukin-2	O
,	O
and	O
RNase	O
H	O
.	O
</s>
<s>
In	O
2008	O
,	O
they	O
used	O
Folding	B-Application
@home	I-Application
to	O
study	O
the	O
interior	O
of	O
this	O
tunnel	O
and	O
how	O
specific	O
molecules	O
may	O
affect	O
it	O
.	O
</s>
<s>
The	O
full	O
structure	O
of	O
the	O
ribosome	O
was	O
determined	O
only	O
as	O
of	O
2011	O
,	O
and	O
Folding	B-Application
@home	I-Application
has	O
also	O
simulated	O
ribosomal	O
proteins	O
,	O
as	O
many	O
of	O
their	O
functions	O
remain	O
largely	O
unknown	O
.	O
</s>
<s>
There	O
are	O
many	O
more	O
protein	O
misfolding	O
promoted	O
diseases	O
that	O
can	O
be	O
benefited	O
from	O
Folding	B-Application
@home	I-Application
to	O
either	O
discern	O
the	O
misfolded	O
protein	O
structure	O
or	O
the	O
misfolding	O
kinetics	O
,	O
and	O
assist	O
in	O
drug	O
design	O
in	O
the	O
future	O
.	O
</s>
<s>
Using	O
the	O
known	O
structure	O
of	O
PrPc	O
and	O
the	O
results	O
of	O
the	O
in	O
vitro	O
and	O
in	O
vivo	O
studies	O
described	O
below	O
,	O
Folding	B-Application
@home	I-Application
could	O
be	O
valuable	O
in	O
elucidating	O
how	O
PrPSc	O
is	O
formed	O
and	O
how	O
the	O
infectious	O
protein	O
arrange	O
themselves	O
to	O
form	O
fibrils	O
and	O
amyloid	O
like	O
plaques	O
,	O
bypassing	O
the	O
requirement	O
to	O
purify	O
PrPSc	O
or	O
dissolve	O
the	O
aggregates	O
.	O
</s>
<s>
The	O
disease	O
causing	O
PrPSc	O
is	O
proteinase	O
K	B-Device
resistant	O
and	O
insoluble	O
.	O
</s>
<s>
Despite	O
the	O
difficulty	O
to	O
purify	O
and	O
characterize	O
PrPSc	O
,	O
from	O
the	O
known	O
molecular	O
structure	O
of	O
PrPc	O
and	O
using	O
transgenic	O
mice	O
and	O
N-terminal	O
deletion	O
,	O
the	O
potential	O
‘	O
hot	O
spots’	O
of	O
protein	O
misfolding	O
leading	O
to	O
the	O
pathogenic	O
PrPSc	O
could	O
be	O
deduced	O
and	O
Folding	B-Application
@home	I-Application
could	O
be	O
of	O
great	O
value	O
in	O
confirming	O
these	O
.	O
</s>
<s>
Like	O
other	O
distributed	B-Operating_System
computing	I-Operating_System
projects	I-Operating_System
,	O
Folding	B-Application
@home	I-Application
is	O
an	O
online	O
citizen	O
science	O
project	O
.	O
</s>
<s>
Folding	B-Application
@home	I-Application
is	O
no	O
different	O
in	O
that	O
respect	O
.	O
</s>
<s>
Research	O
carried	O
out	O
recently	O
on	O
over	O
400	O
active	O
participants	O
revealed	O
that	O
they	O
wanted	O
to	O
help	O
make	O
a	O
contribution	O
to	O
research	O
and	O
that	O
many	O
had	O
friends	O
or	O
relatives	O
affected	O
by	O
the	O
diseases	O
that	O
the	O
Folding	B-Application
@home	I-Application
scientists	O
investigate	O
.	O
</s>
<s>
Folding	B-Application
@home	I-Application
attracts	O
participants	O
who	O
are	O
computer	O
hardware	O
enthusiasts	O
.	O
</s>
<s>
Other	O
distributed	B-Operating_System
computing	I-Operating_System
projects	I-Operating_System
attract	O
these	O
types	O
of	O
participants	O
and	O
projects	O
are	O
often	O
used	O
to	O
benchmark	O
the	O
performance	O
of	O
modified	O
computers	O
,	O
and	O
this	O
aspect	O
of	O
the	O
hobby	O
is	O
accommodated	O
through	O
the	O
competitive	O
nature	O
of	O
the	O
project	O
.	O
</s>
<s>
Individuals	O
and	O
teams	O
can	O
compete	O
to	O
see	O
who	O
can	O
process	O
the	O
most	O
computer	O
processing	O
units	O
(	O
CPUs	B-Device
)	O
.	O
</s>
<s>
This	O
latest	O
research	O
on	O
Folding	B-Application
@home	I-Application
involving	O
interview	O
and	O
ethnographic	O
observation	O
of	O
online	O
groups	O
showed	O
that	O
teams	O
of	O
hardware	O
enthusiasts	O
can	O
sometimes	O
work	O
together	O
,	O
sharing	O
best	O
practice	O
with	O
regard	O
to	O
maximizing	O
processing	O
output	O
.	O
</s>
<s>
This	O
pattern	O
of	O
participation	O
has	O
been	O
observed	O
in	O
other	O
distributed	B-Operating_System
computing	I-Operating_System
projects	I-Operating_System
.	O
</s>
<s>
Another	O
key	O
observation	O
of	O
Folding	B-Application
@home	I-Application
participants	O
is	O
that	O
many	O
are	O
male	O
.	O
</s>
<s>
Not	O
all	O
Folding	B-Application
@home	I-Application
participants	O
are	O
hardware	O
enthusiasts	O
.	O
</s>
<s>
Supercomputer	B-Architecture
FLOPS	O
performance	O
is	O
assessed	O
by	O
running	O
the	O
legacy	O
LINPACK	B-Application
benchmark	O
.	O
</s>
<s>
This	O
short-term	O
testing	O
has	O
difficulty	O
in	O
accurately	O
reflecting	O
sustained	O
performance	O
on	O
real-world	O
tasks	O
because	O
LINPACK	B-Application
more	O
efficiently	O
maps	O
to	O
supercomputer	B-Architecture
hardware	O
.	O
</s>
<s>
Despite	O
this	O
,	O
FLOPS	O
remain	O
the	O
primary	O
speed	O
metric	O
used	O
in	O
supercomputing	B-Architecture
.	O
</s>
<s>
In	O
contrast	O
,	O
Folding	B-Application
@home	I-Application
determines	O
its	O
FLOPS	O
using	O
wall-clock	B-General_Concept
time	I-General_Concept
by	O
measuring	O
how	O
much	O
time	O
its	O
work	O
units	O
take	O
to	O
complete	O
.	O
</s>
<s>
On	O
September	O
16	O
,	O
2007	O
,	O
due	O
in	O
large	O
part	O
to	O
the	O
participation	O
of	O
PlayStation	B-Operating_System
3	I-Operating_System
consoles	O
,	O
the	O
Folding	B-Application
@home	I-Application
project	O
officially	O
attained	O
a	O
sustained	O
performance	O
level	O
higher	O
than	O
one	O
native	O
petaFLOPS	B-General_Concept
,	O
becoming	O
the	O
first	O
computing	O
system	O
of	O
any	O
kind	O
to	O
do	O
so	O
.	O
</s>
<s>
Top500	B-Operating_System
's	O
fastest	B-Operating_System
supercomputer	I-Operating_System
at	O
the	O
time	O
was	O
BlueGene/L	B-Operating_System
,	O
at	O
0.280	O
petaFLOPS	B-General_Concept
.	O
</s>
<s>
The	O
following	O
year	O
,	O
on	O
May	O
7	O
,	O
2008	O
,	O
the	O
project	O
attained	O
a	O
sustained	O
performance	O
level	O
higher	O
than	O
two	O
native	O
petaFLOPS	B-General_Concept
,	O
followed	O
by	O
the	O
three	O
and	O
four	O
native	O
petaFLOPS	B-General_Concept
milestones	O
in	O
August	O
2008	O
and	O
September	O
28	O
,	O
2008	O
respectively	O
.	O
</s>
<s>
On	O
February	O
18	O
,	O
2009	O
,	O
Folding	B-Application
@home	I-Application
achieved	O
five	O
native	O
petaFLOPS	B-General_Concept
,	O
and	O
was	O
the	O
first	O
computing	O
project	O
to	O
meet	O
these	O
five	O
levels	O
.	O
</s>
<s>
In	O
comparison	O
,	O
November	O
2008	O
's	O
fastest	B-Operating_System
supercomputer	I-Operating_System
was	O
IBM	O
's	O
Roadrunner	B-General_Concept
at	O
1.105	O
petaFLOPS	B-General_Concept
.	O
</s>
<s>
On	O
November	O
10	O
,	O
2011	O
,	O
home	O
's	O
performance	O
exceeded	O
six	O
native	O
petaFLOPS	B-General_Concept
with	O
the	O
equivalent	O
of	O
nearly	O
eight	O
x86	O
petaFLOPS	B-General_Concept
.	O
</s>
<s>
In	O
mid-May	O
2013	O
,	O
Folding	B-Application
@home	I-Application
attained	O
over	O
seven	O
native	O
petaFLOPS	B-General_Concept
,	O
with	O
the	O
equivalent	O
of	O
14.87	O
x86	O
petaFLOPS	B-General_Concept
.	O
</s>
<s>
It	O
then	O
reached	O
eight	O
native	O
petaFLOPS	B-General_Concept
on	O
June	O
21	O
,	O
followed	O
by	O
nine	O
on	O
September	O
9	O
of	O
that	O
year	O
,	O
with	O
17.9	O
x86	O
petaFLOPS	B-General_Concept
.	O
</s>
<s>
On	O
May	O
11	O
,	O
2016	O
Folding	B-Application
@home	I-Application
announced	O
that	O
it	O
was	O
moving	O
towards	O
reaching	O
the	O
100	O
x86	O
petaFLOPS	B-General_Concept
mark	O
.	O
</s>
<s>
On	O
March	O
20	O
,	O
2020	O
Folding	B-Application
@home	I-Application
announced	O
via	O
Twitter	O
that	O
it	O
was	O
running	O
with	O
over	O
470	O
native	O
petaFLOPS	B-General_Concept
,	O
the	O
equivalent	O
of	O
958	O
x86	O
petaFLOPS	B-General_Concept
.	O
</s>
<s>
By	O
March	O
25	O
it	O
reached	O
768	O
petaFLOPS	B-General_Concept
,	O
or	O
1.5	O
x86	O
exaFLOPS	O
,	O
making	O
it	O
the	O
first	O
exaFLOP	B-General_Concept
computing	I-General_Concept
system	I-General_Concept
.	O
</s>
<s>
On	O
November	O
20	O
,	O
2020	O
Folding	B-Application
@home	I-Application
only	O
has	O
0.2	O
x86	O
exaFLOPS	O
due	O
to	O
a	O
calculation	O
error	O
.	O
</s>
<s>
Similarly	O
to	O
other	O
distributed	B-Operating_System
computing	I-Operating_System
projects	I-Operating_System
,	O
Folding	B-Application
@home	I-Application
quantitatively	O
assesses	O
user	O
computing	O
contributions	O
to	O
the	O
project	O
through	O
a	O
credit	O
system	O
.	O
</s>
<s>
In	O
some	O
cases	O
,	O
a	O
team	O
may	O
have	O
their	O
own	O
community-driven	O
sources	O
of	O
help	O
or	O
recruitment	O
such	O
as	O
an	O
Internet	B-Application
forum	I-Application
.	O
</s>
<s>
Individual	O
and	O
team	O
statistics	O
are	O
posted	O
on	O
the	O
Folding	B-Application
@home	I-Application
website	O
.	O
</s>
<s>
Folding	B-Application
@home	I-Application
software	O
at	O
the	O
user	O
's	O
end	O
involves	O
three	O
primary	O
components	O
:	O
work	O
units	O
,	O
cores	O
,	O
and	O
a	O
client	B-Protocol
.	O
</s>
<s>
A	O
work	O
unit	O
is	O
the	O
protein	O
data	O
that	O
the	O
client	B-Protocol
is	O
asked	O
to	O
process	O
.	O
</s>
<s>
After	O
the	O
work	O
unit	O
has	O
been	O
downloaded	O
and	O
completely	O
processed	O
by	O
a	O
volunteer	O
's	O
computer	O
,	O
it	O
is	O
returned	O
to	O
Folding	B-Application
@home	I-Application
servers	O
,	O
which	O
then	O
award	O
the	O
volunteer	O
the	O
credit	O
points	O
.	O
</s>
<s>
Due	O
to	O
these	O
deadlines	O
,	O
the	O
minimum	O
system	O
requirement	O
for	O
Folding	B-Application
@home	I-Application
is	O
a	O
Pentium3	O
450MHz	O
CPU	B-Device
with	O
Streaming	B-General_Concept
SIMD	I-General_Concept
Extensions	I-General_Concept
(	O
SSE	O
)	O
.	O
</s>
<s>
However	O
,	O
work	O
units	O
for	O
high-performance	O
clients	O
have	O
a	O
much	O
shorter	O
deadline	O
than	O
those	O
for	O
the	O
uniprocessor	B-Operating_System
client	B-Protocol
,	O
as	O
a	O
major	O
part	O
of	O
the	O
scientific	O
benefit	O
is	O
dependent	O
on	O
rapidly	O
completing	O
simulations	O
.	O
</s>
<s>
These	O
testing	O
stages	O
include	O
internal	O
,	O
beta	O
,	O
and	O
advanced	O
,	O
before	O
a	O
final	O
full	O
release	O
across	O
Folding	B-Application
@home	I-Application
.	O
</s>
<s>
The	O
Folding	B-Application
@home	I-Application
support	O
forum	O
can	O
be	O
used	O
to	O
differentiate	O
between	O
issues	O
arising	O
from	O
problematic	O
hardware	O
and	O
bad	O
work	O
units	O
.	O
</s>
<s>
Specialized	O
molecular	O
dynamics	O
programs	O
,	O
referred	O
to	O
as	O
"	O
FahCores	O
"	O
and	O
often	O
abbreviated	O
"	O
cores	O
"	O
,	O
perform	O
the	O
calculations	O
on	O
the	O
work	O
unit	O
as	O
a	O
background	B-Operating_System
process	I-Operating_System
.	O
</s>
<s>
A	O
large	O
majority	O
of	O
home	O
's	O
cores	O
are	O
based	O
on	O
GROMACS	B-Application
,	O
one	O
of	O
the	O
fastest	O
and	O
most	O
popular	O
molecular	O
dynamics	O
software	O
packages	O
,	O
which	O
largely	O
consists	O
of	O
manually	O
optimized	O
assembly	B-Language
language	I-Language
code	O
and	O
hardware	O
optimizations	O
.	O
</s>
<s>
Although	O
GROMACS	B-Application
is	O
open-source	B-Application
software	I-Application
and	O
there	O
is	O
a	O
cooperative	O
effort	O
between	O
the	O
Pande	O
lab	O
and	O
GROMACS	B-Application
developers	O
,	O
Folding	B-Application
@home	I-Application
uses	O
a	O
closed-source	B-Application
license	O
to	O
help	O
ensure	O
data	O
validity	O
.	O
</s>
<s>
Folding	B-Application
@home	I-Application
has	O
used	O
AMBER	B-Device
,	O
CPMD	B-Application
,	O
Desmond	B-Application
,	O
and	O
TINKER	B-Application
,	O
but	O
these	O
have	O
since	O
been	O
retired	O
and	O
are	O
no	O
longer	O
in	O
active	O
service	O
.	O
</s>
<s>
The	O
core	O
is	O
separate	O
from	O
the	O
client	B-Protocol
to	O
enable	O
the	O
scientific	O
methods	O
to	O
be	O
updated	O
automatically	O
without	O
requiring	O
a	O
client	B-Protocol
update	O
.	O
</s>
<s>
The	O
cores	O
periodically	O
create	O
calculation	O
checkpoints	B-General_Concept
so	O
that	O
if	O
they	O
are	O
interrupted	O
they	O
can	O
resume	O
work	O
from	O
that	O
point	O
upon	O
startup	O
.	O
</s>
<s>
A	O
Folding	B-Application
@home	I-Application
participant	O
installs	O
a	O
client	B-Protocol
program	I-Protocol
on	O
their	O
personal	B-Device
computer	I-Device
.	O
</s>
<s>
The	O
user	O
interacts	O
with	O
the	O
client	B-Protocol
,	O
which	O
manages	O
the	O
other	O
software	O
components	O
in	O
the	O
background	B-Operating_System
.	O
</s>
<s>
Through	O
the	O
client	B-Protocol
,	O
the	O
user	O
may	O
pause	O
the	O
folding	O
process	O
,	O
open	O
an	O
event	O
log	O
,	O
check	O
the	O
work	O
progress	O
,	O
or	O
view	O
personal	O
statistics	O
.	O
</s>
<s>
The	O
computer	O
clients	O
run	O
continuously	O
in	O
the	O
background	B-Operating_System
at	O
a	O
very	O
low	O
priority	O
,	O
using	O
idle	O
processing	O
power	O
so	O
that	O
normal	O
computer	O
use	O
is	O
unaffected	O
.	O
</s>
<s>
The	O
maximum	O
CPU	B-Device
use	O
can	O
be	O
adjusted	O
via	O
client	B-Protocol
settings	O
.	O
</s>
<s>
The	O
client	B-Protocol
connects	O
to	O
a	O
Folding	B-Application
@home	I-Application
server	B-Application
and	O
retrieves	O
a	O
work	O
unit	O
and	O
may	O
also	O
download	O
the	O
appropriate	O
core	O
for	O
the	O
client	B-Protocol
's	O
settings	O
,	O
operating	O
system	O
,	O
and	O
the	O
underlying	O
hardware	O
architecture	O
.	O
</s>
<s>
After	O
processing	O
,	O
the	O
work	O
unit	O
is	O
returned	O
to	O
the	O
Folding	B-Application
@home	I-Application
servers	O
.	O
</s>
<s>
Computer	O
clients	O
are	O
tailored	O
to	O
uniprocessor	B-Operating_System
and	O
multi-core	B-Architecture
processor	I-Architecture
systems	O
,	O
and	O
graphics	B-Architecture
processing	I-Architecture
units	I-Architecture
.	O
</s>
<s>
The	O
diversity	O
and	O
power	O
of	O
each	O
hardware	O
architecture	O
provides	O
Folding	B-Application
@home	I-Application
with	O
the	O
ability	O
to	O
efficiently	O
complete	O
many	O
types	O
of	O
simulations	O
in	O
a	O
timely	O
manner	O
(	O
in	O
a	O
few	O
weeks	O
or	O
months	O
rather	O
than	O
years	O
)	O
,	O
which	O
is	O
of	O
significant	O
scientific	O
value	O
.	O
</s>
<s>
Professional	O
software	O
developers	O
are	O
responsible	O
for	O
most	O
of	O
home	O
's	O
code	O
,	O
both	O
for	O
the	O
client	B-Protocol
and	O
server-side	O
.	O
</s>
<s>
Clients	O
can	O
be	O
downloaded	O
only	O
from	O
the	O
official	O
Folding	B-Application
@home	I-Application
website	O
or	O
its	O
commercial	O
partners	O
,	O
and	O
will	O
only	O
interact	O
with	O
Folding	B-Application
@home	I-Application
computer	O
files	O
.	O
</s>
<s>
While	O
the	O
client	B-Protocol
's	O
graphical	B-Application
user	I-Application
interface	I-Application
(	O
GUI	B-Application
)	O
is	O
open-source	B-Application
,	O
the	O
client	B-Protocol
is	O
proprietary	B-Application
software	I-Application
citing	O
security	O
and	O
scientific	O
integrity	O
as	O
the	O
reasons	O
.	O
</s>
<s>
However	O
,	O
this	O
rationale	O
of	O
using	O
proprietary	B-Application
software	I-Application
is	O
disputed	O
since	O
while	O
the	O
license	O
could	O
be	O
enforceable	O
in	O
the	O
legal	O
domain	O
retrospectively	O
,	O
it	O
does	O
n't	O
practically	O
prevent	O
the	O
modification	O
(	O
also	O
known	O
as	O
patching	O
)	O
of	O
the	O
executable	O
binary	O
files	O
.	O
</s>
<s>
Likewise	O
,	O
binary-only	B-Application
distribution	O
does	O
not	O
prevent	O
the	O
malicious	O
modification	O
of	O
executable	O
binary-code	O
,	O
either	O
through	O
a	O
man-in-the-middle	O
attack	O
while	O
being	O
downloaded	O
via	O
the	O
internet	O
,	O
or	O
by	O
the	O
redistribution	O
of	O
binaries	O
by	O
a	O
third-party	O
that	O
have	O
been	O
previously	O
modified	O
either	O
in	O
their	O
binary	O
state	O
(	O
i.e.	O
</s>
<s>
Either	O
way	O
,	O
since	O
in	O
the	O
case	O
of	O
Folding	B-Application
@home	I-Application
the	O
input	O
data	O
and	O
output	O
result	O
processed	O
by	O
the	O
client-software	O
are	O
both	O
digitally	O
signed	O
,	O
the	O
integrity	O
of	O
work	O
can	O
be	O
verified	O
independently	O
from	O
the	O
integrity	O
of	O
the	O
client	B-Protocol
software	I-Protocol
itself	O
.	O
</s>
<s>
Folding	B-Application
@home	I-Application
uses	O
the	O
Cosm	B-Operating_System
software	B-Library
libraries	I-Library
for	O
networking	O
.	O
</s>
<s>
Folding	B-Application
@home	I-Application
was	O
launched	O
on	O
October1	O
,	O
2000	O
,	O
and	O
was	O
the	O
first	O
distributed	B-Operating_System
computing	I-Operating_System
project	I-Operating_System
aimed	O
at	O
bio-molecular	O
systems	O
.	O
</s>
<s>
Its	O
first	O
client	B-Protocol
was	O
a	O
screensaver	B-General_Concept
,	O
which	O
would	O
run	O
while	O
the	O
computer	O
was	O
not	O
otherwise	O
in	O
use	O
.	O
</s>
<s>
In	O
2004	O
,	O
the	O
Pande	O
lab	O
collaborated	O
with	O
David	O
P	O
.	O
Anderson	O
to	O
test	O
a	O
supplemental	O
client	B-Protocol
on	O
the	O
open-source	B-Application
BOINC	B-Operating_System
framework	O
.	O
</s>
<s>
This	O
client	B-Protocol
was	O
released	O
to	O
closed	O
beta	O
in	O
April	O
2005	O
;	O
however	O
,	O
the	O
method	O
became	O
unworkable	O
and	O
was	O
shelved	O
in	O
June	O
2006	O
.	O
</s>
<s>
The	O
specialized	O
hardware	O
of	O
graphics	B-Architecture
processing	I-Architecture
units	I-Architecture
(	O
GPU	B-Architecture
)	O
is	O
designed	O
to	O
accelerate	O
rendering	O
of	O
3-Dgraphics	O
applications	O
such	O
as	O
video	O
games	O
and	O
can	O
significantly	O
outperform	O
CPUs	B-Device
for	O
some	O
types	O
of	O
calculations	O
.	O
</s>
<s>
GPUs	B-Architecture
are	O
one	O
of	O
the	O
most	O
powerful	O
and	O
rapidly	O
growing	O
computing	O
platforms	O
,	O
and	O
many	O
scientists	O
and	O
researchers	O
are	O
pursuing	O
general-purpose	B-Architecture
computing	I-Architecture
on	I-Architecture
graphics	I-Architecture
processing	I-Architecture
units	I-Architecture
(	O
GPGPU	B-Architecture
)	O
.	O
</s>
<s>
However	O
,	O
GPU	B-Architecture
hardware	O
is	O
difficult	O
to	O
use	O
for	O
non-graphics	O
tasks	O
and	O
usually	O
requires	O
significant	O
algorithm	O
restructuring	O
and	O
an	O
advanced	O
understanding	O
of	O
the	O
underlying	O
architecture	O
.	O
</s>
<s>
Folding	B-Application
@home	I-Application
uses	O
the	O
open-source	B-Application
OpenMM	B-Application
library	B-Library
,	O
which	O
uses	O
a	O
bridge	B-Language
design	I-Language
pattern	I-Language
with	O
two	O
application	B-Application
programming	I-Application
interface	I-Application
(	O
API	B-Application
)	O
levels	O
to	O
interface	O
molecular	O
simulation	O
software	O
to	O
an	O
underlying	O
hardware	O
architecture	O
.	O
</s>
<s>
With	O
the	O
addition	O
of	O
hardware	O
optimizations	O
,	O
OpenMM-based	O
GPU	B-Architecture
simulations	O
need	O
no	O
significant	O
modification	O
but	O
achieve	O
performance	O
nearly	O
equal	O
to	O
hand-tuned	O
GPU	B-Architecture
code	O
,	O
and	O
greatly	O
outperform	O
CPU	B-Device
implementations	O
.	O
</s>
<s>
Before	O
2010	O
,	O
the	O
computing	O
reliability	O
of	O
GPGPU	B-Architecture
consumer-grade	O
hardware	O
was	O
largely	O
unknown	O
,	O
and	O
circumstantial	O
evidence	O
related	O
to	O
the	O
lack	O
of	O
built-in	O
error	B-Error_Name
detection	I-Error_Name
and	I-Error_Name
correction	I-Error_Name
in	O
GPU	B-Architecture
memory	O
raised	O
reliability	O
concerns	O
.	O
</s>
<s>
In	O
the	O
first	O
large-scale	O
test	O
of	O
GPU	B-Architecture
scientific	O
accuracy	O
,	O
a	O
2010	O
study	O
of	O
over	O
20,000	O
hosts	O
on	O
the	O
Folding	B-Application
@home	I-Application
network	O
detected	O
soft	O
errors	O
in	O
the	O
memory	O
subsystems	O
of	O
two-thirds	O
of	O
the	O
tested	O
GPUs	B-Architecture
.	O
</s>
<s>
These	O
errors	O
strongly	O
correlated	O
to	O
board	O
architecture	O
,	O
though	O
the	O
study	O
concluded	O
that	O
reliable	O
GPU	B-Architecture
computing	I-Architecture
was	O
very	O
feasible	O
as	O
long	O
as	O
attention	O
is	O
paid	O
to	O
the	O
hardware	O
traits	O
,	O
such	O
as	O
software-side	O
error	B-Error_Name
detection	I-Error_Name
.	O
</s>
<s>
The	O
first	O
generation	O
of	O
home	O
's	O
GPU	B-Architecture
client	B-Protocol
(	O
GPU1	O
)	O
was	O
released	O
to	O
the	O
public	O
on	O
October2	O
,	O
2006	O
,	O
delivering	O
a	O
20	O
–	O
30	O
times	O
speedup	O
for	O
some	O
calculations	O
over	O
its	O
CPU-based	O
GROMACS	B-Application
counterparts	O
.	O
</s>
<s>
It	O
was	O
the	O
first	O
time	O
GPUs	B-Architecture
had	O
been	O
used	O
for	O
either	O
distributed	B-Architecture
computing	I-Architecture
or	O
major	O
molecular	O
dynamics	O
calculations	O
.	O
</s>
<s>
GPU1	O
gave	O
researchers	O
significant	O
knowledge	O
and	O
experience	O
with	O
the	O
development	O
of	O
GPGPU	B-Architecture
software	O
,	O
but	O
in	O
response	O
to	O
scientific	O
inaccuracies	O
with	O
DirectX	B-Application
,	O
on	O
April10	O
,	O
2008	O
it	O
was	O
succeeded	O
by	O
GPU2	O
,	O
the	O
second	O
generation	O
of	O
the	O
client	B-Protocol
.	O
</s>
<s>
Compared	O
to	O
GPU1	O
,	O
GPU2	O
was	O
more	O
scientifically	O
reliable	O
and	O
productive	O
,	O
ran	O
on	O
ATI	O
and	O
CUDA-enabled	O
Nvidia	O
GPUs	B-Architecture
,	O
and	O
supported	O
more	O
advanced	O
algorithms	O
,	O
larger	O
proteins	O
,	O
and	O
real-time	O
visualization	O
of	O
the	O
protein	O
simulation	O
.	O
</s>
<s>
Following	O
this	O
,	O
the	O
third	O
generation	O
of	O
home	O
's	O
GPU	B-Architecture
client	B-Protocol
(	O
GPU3	O
)	O
was	O
released	O
on	O
May25	O
,	O
2010	O
.	O
</s>
<s>
While	O
backward	B-General_Concept
compatible	I-General_Concept
with	O
GPU2	O
,	O
GPU3	O
was	O
more	O
stable	O
,	O
efficient	O
,	O
and	O
flexibile	O
in	O
its	O
scientific	O
abilities	O
,	O
and	O
used	O
OpenMM	B-Application
on	O
top	O
of	O
an	O
OpenCL	B-Application
framework	O
.	O
</s>
<s>
Although	O
these	O
GPU3	O
clients	O
did	O
not	O
natively	O
support	O
the	O
operating	O
systems	O
Linux	B-Application
and	O
macOS	B-Application
,	O
Linux	B-Application
users	O
with	O
Nvidia	O
graphics	O
cards	O
were	O
able	O
to	O
run	O
them	O
through	O
the	O
Wine	B-Application
software	I-Application
application	O
.	O
</s>
<s>
GPUs	B-Architecture
remain	O
home	O
's	O
most	O
powerful	O
platform	O
in	O
FLOPS	O
.	O
</s>
<s>
As	O
of	O
November	O
2012	O
,	O
GPU	B-Architecture
clients	O
account	O
for	O
87%	O
of	O
the	O
entire	O
project	O
's	O
x86	O
FLOPS	O
throughput	O
.	O
</s>
<s>
Native	O
support	O
for	O
Nvidia	O
and	O
AMD	O
graphics	O
cards	O
under	O
Linux	B-Application
was	O
introduced	O
with	O
FahCore	O
17	O
,	O
which	O
uses	O
OpenCL	B-Application
rather	O
than	O
CUDA	B-Architecture
.	O
</s>
<s>
From	O
March	O
2007	O
until	O
November	O
2012	O
,	O
Folding	B-Application
@home	I-Application
took	O
advantage	O
of	O
the	O
computing	O
power	O
of	O
PlayStation	B-Operating_System
3s	I-Operating_System
.	O
</s>
<s>
At	O
the	O
time	O
of	O
its	O
inception	O
,	O
its	O
main	O
streaming	B-Application
Cell	B-General_Concept
processor	I-General_Concept
delivered	O
a	O
20	O
times	O
speed	O
increase	O
over	O
PCs	B-Device
for	O
some	O
calculations	O
,	O
processing	O
power	O
which	O
could	O
not	O
be	O
found	O
on	O
other	O
systems	O
such	O
as	O
the	B-Operating_System
Xbox	I-Operating_System
360	I-Operating_System
.	O
</s>
<s>
The	B-Operating_System
PS3	I-Operating_System
's	O
high	O
speed	O
and	O
efficiency	O
introduced	O
other	O
opportunities	O
for	O
worthwhile	O
optimizations	O
according	O
to	O
Amdahl	B-Operating_System
's	I-Operating_System
law	I-Operating_System
,	O
and	O
significantly	O
changed	O
the	O
tradeoff	O
between	O
computing	O
efficiency	O
and	O
overall	O
accuracy	O
,	O
allowing	O
the	O
use	O
of	O
more	O
complex	O
molecular	O
models	O
at	O
little	O
added	O
computing	O
cost	O
.	O
</s>
<s>
This	O
allowed	O
Folding	B-Application
@home	I-Application
to	O
run	O
biomedical	O
calculations	O
that	O
would	O
have	O
been	O
otherwise	O
infeasible	O
computationally	O
.	O
</s>
<s>
The	B-Operating_System
PS3	I-Operating_System
client	B-Protocol
was	O
developed	O
in	O
a	O
collaborative	O
effort	O
between	O
Sony	O
and	O
the	O
Pande	O
lab	O
and	O
was	O
first	O
released	O
as	O
a	O
standalone	O
client	B-Protocol
on	O
March23	O
,	O
2007	O
.	O
</s>
<s>
Its	O
release	O
made	O
Folding	B-Application
@home	I-Application
the	O
first	O
distributed	B-Operating_System
computing	I-Operating_System
project	I-Operating_System
to	O
use	O
PS3s	B-Operating_System
.	O
</s>
<s>
On	O
September18	O
of	O
the	O
following	O
year	O
,	O
the	B-Operating_System
PS3	I-Operating_System
client	B-Protocol
became	O
a	O
channel	O
of	O
Life	B-Application
with	I-Application
PlayStation	I-Application
on	O
its	O
launch	O
.	O
</s>
<s>
In	O
the	O
types	O
of	O
calculations	O
it	O
can	O
perform	O
,	O
at	O
the	O
time	O
of	O
its	O
introduction	O
,	O
the	O
client	B-Protocol
fit	O
in	O
between	O
a	O
CPU	B-Device
's	O
flexibility	O
and	O
a	O
GPU	B-Architecture
's	O
speed	O
.	O
</s>
<s>
However	O
,	O
unlike	O
clients	O
running	O
on	O
personal	B-Device
computers	I-Device
,	O
users	O
were	O
unable	O
to	O
perform	O
other	O
activities	O
on	O
their	O
PS3	B-Operating_System
while	O
running	O
Folding	B-Application
@home	I-Application
.	O
</s>
<s>
The	B-Operating_System
PS3	I-Operating_System
's	O
uniform	O
console	O
environment	O
made	O
technical	B-General_Concept
support	I-General_Concept
easier	O
and	O
made	O
Folding	B-Application
@home	I-Application
more	O
user	B-General_Concept
friendly	I-General_Concept
.	O
</s>
<s>
The	B-Operating_System
PS3	I-Operating_System
also	O
had	O
the	O
ability	O
to	O
stream	O
data	O
quickly	O
to	O
its	O
GPU	B-Architecture
,	O
which	O
was	O
used	O
for	O
real-time	O
atomic-level	O
visualizing	O
of	O
the	O
current	O
protein	O
dynamics	O
.	O
</s>
<s>
On	O
November	O
6	O
,	O
2012	O
,	O
Sony	O
ended	O
support	O
for	O
the	O
Folding	B-Application
@home	I-Application
PS3	B-Operating_System
client	B-Protocol
and	O
other	O
services	O
available	O
under	O
Life	B-Application
with	I-Application
PlayStation	I-Application
.	O
</s>
<s>
Over	O
its	O
lifetime	O
of	O
five	O
years	O
and	O
seven	O
months	O
,	O
more	O
than	O
15	O
million	O
users	O
contributed	O
over	O
100	O
million	O
hours	O
of	O
computing	O
to	O
Folding	B-Application
@home	I-Application
,	O
greatly	O
assisting	O
the	O
project	O
with	O
disease	O
research	O
.	O
</s>
<s>
Pande	O
considered	O
the	O
PlayStation	B-Operating_System
3	I-Operating_System
client	B-Protocol
a	O
"	O
game	O
changer	O
"	O
for	O
the	O
project	O
.	O
</s>
<s>
Folding	B-Application
@home	I-Application
can	O
use	O
the	O
parallel	B-Operating_System
computing	I-Operating_System
abilities	O
of	O
modern	O
multi-core	B-Architecture
processors	I-Architecture
.	O
</s>
<s>
The	O
ability	O
to	O
use	O
several	O
CPU	B-Architecture
cores	I-Architecture
simultaneously	O
allows	O
completing	O
the	O
full	O
simulation	O
far	O
faster	O
.	O
</s>
<s>
Working	O
together	O
,	O
these	O
CPU	B-Architecture
cores	I-Architecture
complete	O
single	O
work	O
units	O
proportionately	O
faster	O
than	O
the	O
standard	O
uniprocessor	B-Operating_System
client	B-Protocol
.	O
</s>
<s>
This	O
method	O
is	O
scientifically	O
valuable	O
because	O
it	O
enables	O
much	O
longer	O
simulation	O
trajectories	O
to	O
be	O
performed	O
in	O
the	O
same	O
amount	O
of	O
time	O
,	O
and	O
reduces	O
the	O
traditional	O
difficulties	O
of	O
scaling	B-Architecture
a	O
large	O
simulation	O
to	O
many	O
separate	O
processors	O
.	O
</s>
<s>
A	O
2007	O
publication	O
in	O
the	O
Journal	O
of	O
Molecular	O
Biology	O
relied	O
on	O
multi-core	B-Architecture
processing	O
to	O
simulate	O
the	O
folding	O
of	O
part	O
of	O
the	O
villin	O
protein	O
approximately	O
10	O
times	O
longer	O
than	O
was	O
possible	O
with	O
a	O
single-processor	O
client	B-Protocol
,	O
in	O
agreement	O
with	O
experimental	O
folding	O
rates	O
.	O
</s>
<s>
In	O
November	O
2006	O
,	O
first-generation	O
symmetric	B-Operating_System
multiprocessing	I-Operating_System
(	O
SMP	O
)	O
clients	O
were	O
publicly	O
released	O
for	O
open	O
beta	O
testing	O
,	O
referred	O
to	O
as	O
SMP1	O
.	O
</s>
<s>
These	O
clients	O
used	O
Message	B-Application
Passing	I-Application
Interface	I-Application
(	O
MPI	O
)	O
communication	O
protocols	O
for	O
parallel	B-Operating_System
processing	I-Operating_System
,	O
as	O
at	O
that	O
time	O
the	O
GROMACS	B-Application
cores	O
were	O
not	B-Operating_System
designed	I-Operating_System
to	O
be	O
used	O
with	O
multiple	O
threads	B-Operating_System
.	O
</s>
<s>
This	O
was	O
the	O
first	O
time	O
a	O
distributed	B-Operating_System
computing	I-Operating_System
project	I-Operating_System
had	O
used	O
MPI	O
.	O
</s>
<s>
Although	O
the	O
clients	O
performed	O
well	O
in	O
Unix-based	O
operating	O
systems	O
such	O
as	O
Linux	B-Application
and	O
macOS	B-Application
,	O
they	O
were	O
troublesome	O
under	O
Windows	B-Application
.	O
</s>
<s>
On	O
January24	O
,	O
2010	O
,	O
SMP2	O
,	O
the	O
second	O
generation	O
of	O
the	O
SMP	O
clients	O
and	O
the	O
successor	O
to	O
SMP1	O
,	O
was	O
released	O
as	O
an	O
open	O
beta	O
and	O
replaced	O
the	O
complex	O
MPI	O
with	O
a	O
more	O
reliable	O
thread-based	O
implementation	O
.	O
</s>
<s>
These	O
units	O
originally	O
required	O
a	O
minimum	O
of	O
eight	O
CPU	B-Architecture
cores	I-Architecture
,	O
which	O
was	O
raised	O
to	O
sixteen	O
later	O
,	O
on	O
February7	O
,	O
2012	O
.	O
</s>
<s>
Along	O
with	O
these	O
added	O
hardware	O
requirements	O
over	O
standard	O
SMP2	O
work	O
units	O
,	O
they	O
require	O
more	O
system	O
resources	O
such	O
as	O
random-access	B-Architecture
memory	I-Architecture
(	O
RAM	B-Architecture
)	O
and	O
Internet	O
bandwidth	O
.	O
</s>
<s>
The	O
bigadv	O
category	O
allows	O
Folding	B-Application
@home	I-Application
to	O
run	O
especially	O
demanding	O
simulations	O
for	O
long	O
times	O
that	O
had	O
formerly	O
required	O
use	O
of	O
supercomputing	B-Architecture
clusters	O
and	O
could	O
not	O
be	O
performed	O
anywhere	O
else	O
on	O
Folding	B-Application
@home	I-Application
.	O
</s>
<s>
Many	O
users	O
with	O
hardware	O
able	O
to	O
run	O
bigadv	O
units	O
have	O
later	O
had	O
their	O
hardware	O
setup	O
deemed	O
ineligible	O
for	O
bigadv	O
work	O
units	O
when	O
CPU	B-Architecture
core	I-Architecture
minimums	O
were	O
increased	O
,	O
leaving	O
them	O
only	O
able	O
to	O
run	O
the	O
normal	O
SMP	O
work	O
units	O
.	O
</s>
<s>
This	O
frustrated	O
many	O
users	O
who	O
invested	O
significant	O
amounts	O
of	O
money	O
into	O
the	O
program	B-Application
only	O
to	O
have	O
their	O
hardware	O
be	O
obsolete	O
for	O
bigadv	O
purposes	O
shortly	O
after	O
.	O
</s>
<s>
As	O
a	O
result	O
,	O
Pande	O
announced	O
in	O
January	O
2014	O
that	O
the	O
bigadv	O
program	B-Application
would	O
end	O
on	O
January	O
31	O
,	O
2015	O
.	O
</s>
<s>
The	O
V7	O
client	B-Protocol
is	O
the	O
seventh	O
and	O
latest	O
generation	O
of	O
the	O
Folding	B-Application
@home	I-Application
client	B-Protocol
software	I-Protocol
,	O
and	O
is	O
a	O
full	O
rewrite	O
and	O
unification	O
of	O
the	O
prior	O
clients	O
for	O
Windows	B-Application
,	O
macOS	B-Application
,	O
and	O
Linux	B-Application
operating	I-Application
systems	I-Application
.	O
</s>
<s>
Like	O
its	O
predecessors	O
,	O
V7	O
can	O
run	O
Folding	B-Application
@home	I-Application
in	O
the	O
background	B-Operating_System
at	O
a	O
very	O
low	O
priority	O
,	O
allowing	O
other	O
applications	O
to	O
use	O
CPU	B-Device
resources	O
as	O
they	O
need	O
.	O
</s>
<s>
It	O
is	O
designed	O
to	O
make	O
the	O
installation	O
,	O
start-up	O
,	O
and	O
operation	O
more	O
user-friendly	B-General_Concept
for	O
novices	O
,	O
and	O
offer	O
greater	O
scientific	O
flexibility	O
to	O
researchers	O
than	O
prior	O
clients	O
.	O
</s>
<s>
V7	O
uses	O
Trac	B-Language
for	O
managing	B-Application
its	I-Application
bug	I-Application
tickets	I-Application
so	O
that	O
users	O
can	O
see	O
its	O
development	O
process	O
and	O
provide	O
feedback	O
.	O
</s>
<s>
The	O
user	O
typically	O
interacts	O
with	O
V7	O
's	O
open-source	B-Application
GUI	B-Application
,	O
named	O
FAHControl	O
.	O
</s>
<s>
FAHControl	O
directs	O
FAHClient	O
,	O
a	O
back-end	B-Application
application	O
that	O
in	O
turn	O
manages	O
each	O
FAHSlot	O
(	O
or	O
slot	O
)	O
.	O
</s>
<s>
Each	O
slot	O
acts	O
as	O
replacement	O
for	O
the	O
formerly	O
distinct	O
Folding	B-Application
@home	I-Application
v6	O
uniprocessor	B-Operating_System
,	O
SMP	O
,	O
or	O
GPU	B-Architecture
computer	O
clients	O
,	O
as	O
it	O
can	O
download	O
,	O
process	O
,	O
and	O
upload	O
work	O
units	O
independently	O
.	O
</s>
<s>
The	O
FAHViewer	O
function	O
,	O
modeled	O
after	O
the	B-Operating_System
PS3	I-Operating_System
's	O
viewer	O
,	O
displays	O
a	O
real-time	O
3-D	O
rendering	O
,	O
if	O
available	O
,	O
of	O
the	O
protein	O
currently	O
being	O
processed	O
.	O
</s>
<s>
In	O
2014	O
,	O
a	O
client	B-Protocol
for	O
the	B-Application
Google	I-Application
Chrome	B-Application
and	O
Chromium	B-Language
web	I-Language
browsers	I-Language
was	O
released	O
,	O
allowing	O
users	O
to	O
run	O
Folding	B-Application
@home	I-Application
in	O
their	O
web	O
browser	O
.	O
</s>
<s>
The	O
client	B-Protocol
used	O
Google	B-Application
's	I-Application
Native	B-Application
Client	I-Application
(	O
NaCl	B-Application
)	O
feature	O
on	O
Chromium-based	O
web	O
browsers	O
to	O
run	O
the	O
Folding	B-Application
@home	I-Application
code	O
at	O
near-native	O
speed	O
in	O
a	O
sandbox	O
on	O
the	O
user	O
's	O
machine	O
.	O
</s>
<s>
Due	O
to	O
the	O
phasing	O
out	O
of	O
NaCL	B-Application
and	O
changes	O
at	O
Folding	B-Application
@home	I-Application
,	O
the	O
web	O
client	B-Protocol
was	O
permanently	O
shut	O
down	O
in	O
June	O
2019	O
.	O
</s>
<s>
In	O
July	O
2015	O
,	O
a	O
client	B-Protocol
for	O
Android	B-Application
mobile	I-Application
phones	I-Application
was	O
released	O
on	O
Google	B-Application
Play	I-Application
for	O
devices	O
running	O
Android	B-Application
4.4	I-Application
KitKat	I-Application
or	O
newer	O
.	O
</s>
<s>
On	O
February	O
16	O
,	O
2018	O
the	O
Android	B-Application
client	I-Application
,	O
which	O
was	O
offered	O
in	O
cooperation	O
with	O
Sony	O
,	O
was	O
removed	O
from	O
Google	B-Application
Play	I-Application
.	O
</s>
<s>
Rosetta	B-Operating_System
@home	I-Operating_System
is	O
a	O
distributed	B-Operating_System
computing	I-Operating_System
project	I-Operating_System
aimed	O
at	O
protein	O
structure	O
prediction	O
and	O
is	O
one	O
of	O
the	O
most	O
accurate	O
tertiary	O
structure	O
predictors	O
.	O
</s>
<s>
The	O
conformational	O
states	O
from	O
Rosetta	O
's	O
software	O
can	O
be	O
used	O
to	O
initialize	O
a	O
Markov	O
state	O
model	O
as	O
starting	O
points	O
for	O
Folding	B-Application
@home	I-Application
simulations	O
.	O
</s>
<s>
As	O
Rosetta	O
only	O
tries	O
to	O
predict	O
the	O
final	O
folded	O
state	O
,	O
and	O
not	O
how	O
folding	O
proceeds	O
,	O
Rosetta	B-Operating_System
@home	I-Operating_System
and	O
Folding	B-Application
@home	I-Application
are	O
complementary	O
and	O
address	O
very	O
different	O
molecular	O
questions	O
.	O
</s>
<s>
Anton	B-Device
is	O
a	O
special-purpose	O
supercomputer	B-Architecture
built	O
for	O
molecular	O
dynamics	O
simulations	O
.	O
</s>
<s>
In	O
October	O
2011	O
,	O
Anton	B-Device
and	O
Folding	B-Application
@home	I-Application
were	O
the	O
two	O
most	O
powerful	O
molecular	O
dynamics	O
systems	O
.	O
</s>
<s>
Anton	B-Device
is	O
unique	O
in	O
its	O
ability	O
to	O
produce	O
single	O
ultra-long	O
computationally	B-General_Concept
costly	I-General_Concept
molecular	O
trajectories	O
,	O
such	O
as	O
one	O
in	O
2010	O
which	O
reached	O
the	O
millisecond	O
range	O
.	O
</s>
<s>
However	O
,	O
Anton	B-Device
does	O
not	O
use	O
Markov	O
state	O
models	O
(	O
MSM	O
)	O
for	O
analysis	O
.	O
</s>
<s>
In	O
2011	O
,	O
the	O
Pande	O
lab	O
constructed	O
a	O
MSM	O
from	O
two	O
100-µs	O
Anton	B-Device
simulations	O
and	O
found	O
alternative	O
folding	O
pathways	O
that	O
were	O
not	O
visible	O
through	O
Anton	B-Device
's	O
traditional	O
analysis	O
.	O
</s>
<s>
In	O
June	O
2011	O
Folding	B-Application
@home	I-Application
added	O
sampling	O
of	O
an	O
Anton	B-Device
simulation	O
in	O
an	O
effort	O
to	O
better	O
determine	O
how	O
its	O
methods	O
compare	O
to	O
Anton	B-Device
's	O
.	O
</s>
<s>
However	O
,	O
unlike	O
home	O
's	O
shorter	O
trajectories	O
,	O
which	O
are	O
more	O
amenable	O
to	O
distributed	B-Architecture
computing	I-Architecture
and	O
other	O
parallelizing	O
methods	O
,	O
longer	O
trajectories	O
do	O
not	O
require	O
adaptive	O
sampling	O
to	O
sufficiently	O
sample	O
the	O
protein	O
's	O
phase	O
space	O
.	O
</s>
<s>
Due	O
to	O
this	O
,	O
it	O
is	O
possible	O
that	O
a	O
combination	O
of	O
Anton	B-Device
's	O
and	O
home	O
's	O
simulation	O
methods	O
would	O
provide	O
a	O
more	O
thorough	O
sampling	O
of	O
this	O
space	O
.	O
</s>
