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at
lev
er
a
g
es
Py
th
o
n
t
o
s
p
ee
d
u
p
th
e
d
r
u
g
d
is
co
v
er
y
s
y
s
te
m
.
T
h
is
tech
n
i
q
u
e
in
clu
d
es,
am
o
n
g
s
t
d
if
f
er
e
n
t
th
in
g
s
,
tar
g
et
s
elec
tio
n
,
v
al
id
atio
n
,
m
o
lec
u
lar
d
o
ck
in
g
,
v
i
r
tu
al
s
cr
ee
n
in
g
,
a
n
d
im
m
o
d
er
ate
p
h
ar
m
ac
o
k
in
eti
c
ass
ess
m
en
t
[
1
2
]
–
[
1
4
]
.
T
h
e
u
s
e
o
f
Py
th
o
n
o
n
th
is
p
r
o
b
lem
atic
s
y
s
tem
tar
g
ets
to
b
o
o
m
t
h
e
ch
a
n
ce
o
f
co
m
in
g
a
cr
o
s
s
p
o
wer
f
u
l
l
u
n
g
ca
n
ce
r
d
r
u
g
tr
ea
tm
en
ts
ev
e
n
as
d
ec
r
ea
s
in
g
t
h
e
m
o
n
ey
an
d
t
im
e
lo
s
t
o
n
d
r
u
g
d
is
co
v
er
y
.
R
esear
ch
er
s
an
d
p
h
a
r
m
ac
eu
tical
s
p
ec
ialis
ts
ca
n
u
s
e
th
is
p
ap
er
as
a
m
an
u
al
to
h
elp
th
em
m
ak
e
th
e
m
ax
im
u
m
o
f
Py
th
o
n
an
d
in
s
ilico
d
r
u
g
i
m
p
r
o
v
e
m
en
t
in
th
e
co
m
b
at
to
war
d
s
lu
n
g
ca
n
ce
r
a
n
d
to
e
n
h
an
ce
p
atien
t o
u
tc
o
m
e
s
[
1
5
]
–
[
1
9
]
.
S
i
n
c
e
l
u
n
g
c
a
n
c
e
r
h
a
s
a
c
h
i
e
f
e
f
f
e
c
t
o
n
p
u
b
l
i
c
h
e
a
l
t
h
,
i
t
'
s
f
a
r
d
e
f
i
n
i
t
e
l
y
i
m
p
o
r
t
a
n
t
t
o
c
r
e
a
t
e
n
e
w
a
n
d
p
o
w
e
r
f
u
l
d
r
u
g
s
.
F
i
n
d
i
n
g
s
p
e
c
i
a
l
i
z
e
d
t
r
e
a
t
m
e
n
t
s
t
r
a
t
e
g
i
e
s
i
s
c
r
u
c
i
a
l
s
e
e
i
n
g
t
h
a
t
l
u
n
g
c
a
n
c
e
r
i
s
a
v
a
i
l
a
b
l
e
i
n
a
w
h
o
l
e
l
o
t
o
f
f
o
r
m
s
,
e
v
e
r
y
w
i
t
h
w
o
n
d
e
r
f
u
l
g
e
n
e
t
i
c
a
n
d
m
o
l
e
c
u
l
a
r
c
h
a
r
a
c
t
e
r
i
s
t
i
c
s
[
2
0
]
–
[
2
3
]
.
T
r
a
d
i
t
i
o
n
a
l
d
r
u
g
i
m
p
r
o
v
e
m
e
n
t
s
t
r
a
t
e
g
i
e
s
m
a
y
b
e
h
i
g
h
l
y
p
r
i
c
e
d
a
n
d
t
i
m
e
-
c
o
n
s
u
m
i
n
g
,
a
l
t
h
o
u
g
h
t
h
e
y
'
l
l
w
o
r
k
i
n
c
e
r
t
a
i
n
s
i
t
u
a
t
i
o
n
s
.
O
n
t
h
e
a
l
t
e
r
n
a
t
i
v
e
h
a
n
d
,
t
h
e
s
y
s
t
e
m
o
f
i
n
s
i
l
i
c
o
d
r
u
g
d
i
s
c
o
v
e
r
y
i
s
q
u
i
c
k
e
r
a
n
d
m
u
c
h
l
e
s
s
h
i
g
h
l
y
p
r
i
c
e
d
,
t
a
k
i
n
g
i
n
t
o
c
o
n
s
i
d
e
r
a
t
i
o
n
a
m
e
t
h
o
d
i
c
a
l
a
n
d
d
a
t
a
-
d
r
i
v
e
n
l
o
o
k
f
o
r
c
a
p
a
c
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t
y
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h
e
r
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p
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t
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c
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a
n
d
i
d
a
t
e
s
.
T
h
i
s
a
r
t
i
c
l
e
o
u
t
l
i
n
e
s
t
h
e
m
a
n
n
e
r
f
o
r
a
n
i
n
s
i
l
i
c
o
d
r
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g
i
m
p
r
o
v
e
m
e
n
t
f
r
a
m
e
w
o
r
k
a
n
d
e
m
p
h
a
s
i
z
e
s
t
h
e
v
a
l
u
e
o
f
P
y
t
h
o
n
a
s
a
p
r
o
g
r
a
m
m
i
n
g
l
a
n
g
u
a
g
e
.
P
y
t
h
o
n
`
s
m
a
n
y
t
o
o
l
s
,
f
l
e
x
i
b
i
l
i
t
y
,
a
n
d
s
t
u
r
d
y
n
e
t
w
o
r
k
m
a
k
e
i
t
a
r
e
m
a
r
k
a
b
l
e
p
r
e
f
e
r
e
n
c
e
f
o
r
i
m
p
o
s
i
n
g
m
a
n
y
c
o
m
p
u
t
a
t
i
o
n
a
l
c
o
m
p
o
n
e
n
t
s
o
f
d
r
u
g
s
t
u
d
i
e
s
[
2
4
]
–
[
2
7
]
.
T
h
r
o
u
g
h
t
h
e
c
r
e
a
t
i
o
n
o
f
a
P
y
t
h
o
n
-
b
a
s
e
d
p
l
a
t
f
o
r
m
,
t
h
i
s
o
b
s
e
r
v
e
s
e
e
k
s
t
o
p
e
r
m
i
t
r
e
s
e
a
r
c
h
e
r
s
,
b
i
o
i
n
f
o
r
m
a
t
i
c
i
a
n
s
,
a
n
d
c
o
m
p
u
t
a
t
i
o
n
a
l
b
i
o
l
o
g
i
s
t
s
t
o
a
c
c
e
l
e
r
a
t
e
t
h
e
d
r
u
g
i
m
p
r
o
v
e
m
e
n
t
m
a
n
n
e
r
a
n
d
p
e
r
m
i
t
a
f
a
s
t
e
r
t
r
a
n
s
l
a
t
i
o
n
o
f
s
t
u
d
i
e
s
d
i
s
c
o
v
e
r
i
e
s
i
n
t
o
b
e
n
e
f
i
c
i
a
l
m
e
d
i
c
i
n
e
s
[
2
8
]
.
T
h
e
v
al
u
e
an
d
tim
e
-
i
n
g
esti
n
g
n
atu
r
e
o
f
th
e
tr
ad
itio
n
al
d
r
u
g
d
is
co
v
er
y
tech
n
iq
u
e
ar
e
its
d
r
awb
ac
k
s
.
T
h
e
p
r
im
ar
y
aim
is
to
in
cr
ea
s
e
a
d
r
u
g
d
is
co
v
er
y
p
latf
o
r
m
ta
ilo
r
-
m
ad
e
to
lu
n
g
ca
n
ce
r
,
ad
d
r
ess
in
g
th
is
d
if
f
icu
lt
tr
o
u
b
le
with
in
s
ilico
tech
n
iq
u
es
an
d
th
e
Py
th
o
n
p
r
o
g
r
am
m
i
n
g
lan
g
u
a
g
e.
T
h
e
n
u
m
b
e
r
o
n
e
task
is
g
r
o
win
g
an
in
ten
s
iv
e
in
s
ilico
en
v
ir
o
n
m
e
n
t
th
at
en
co
m
p
ass
es
all
s
tag
es
o
f
th
e
d
r
u
g
im
p
r
o
v
em
e
n
t
tech
n
iq
u
e,
to
g
eth
e
r
with
v
ir
tu
al
s
cr
ee
n
in
g
,
m
o
lecu
la
r
d
o
ck
in
g
,
p
h
ar
m
ac
o
k
i
n
etic
ev
al
u
atio
n
,
tar
g
et
s
elec
tio
n
,
an
d
v
alid
atio
n
[
2
9
]
–
[
3
1
]
.
W
e
d
esire
to
ap
p
o
in
t
Py
t
h
o
n
-
b
as
ed
lib
r
ar
ies,
c
o
m
p
u
tatio
n
al
to
o
ls
,
an
d
m
ac
h
in
e
-
lear
n
in
g
s
tr
ateg
ies
to
g
r
o
wth
th
e
p
er
f
o
r
m
a
n
ce
o
f
th
is
p
r
o
ce
d
u
r
e
[
3
2
]
,
[
3
3
]
.
T
h
is
wo
r
k
ai
m
s
to
ad
d
r
ess
th
e
u
r
g
en
t
n
ee
d
f
o
r
a
Py
th
o
n
-
d
r
iv
en
,
tim
e
-
ef
f
icien
t,
an
d
c
o
s
t
-
ef
f
ec
ti
v
e
d
r
u
g
d
is
co
v
er
y
f
r
am
ewo
r
k
to
f
in
d
au
s
p
icio
u
s
th
er
ap
eu
tic
ca
n
d
id
ates
f
o
r
th
e
d
ea
lin
g
o
f
l
u
n
g
ca
n
ce
r
.
T
h
e
u
lt
im
ate
o
b
jectiv
e
is
to
u
s
e
Py
th
o
n
'
s
s
tr
en
g
th
s
in
s
i
lico
d
r
u
g
d
is
co
v
er
y
t
o
s
p
ee
d
u
p
th
e
cr
ea
tio
n
o
f
n
ew
lu
n
g
ca
n
ce
r
tr
ea
tm
en
ts
an
d
en
h
an
ce
p
atien
t.
Dr
u
g
d
is
co
v
e
r
y
is
r
eso
u
r
ce
an
d
tim
e
-
co
n
s
u
m
in
g
.
Ov
e
r
all,
th
e
f
r
am
ewo
r
k
en
v
is
io
n
ed
s
ee
k
s
to
r
e
v
o
lu
tio
n
ize
d
r
u
g
d
is
co
v
er
y
p
r
o
ce
s
s
es
s
p
ec
if
ically
f
o
r
lu
n
g
ca
n
ce
r
wh
ile
u
tili
zin
g
th
e
p
o
wer
o
f
Py
th
o
n
an
d
in
s
i
lico
m
eth
o
d
o
lo
g
ies
[
3
4
]
–
[
3
6
]
.
T
h
e
s
u
m
m
ar
y
o
f
th
e
liter
atu
r
e
r
ev
iew
h
as
b
ee
n
s
u
m
m
ar
iz
ed
in
T
ab
le
1
.
i)
T
h
e
r
esear
c
h
er
s
h
av
e
o
b
s
er
v
ed
th
at
p
atien
ts
d
iag
n
o
s
ed
with
L
u
n
g
ca
n
ce
r
o
f
te
n
f
ac
e
ch
allen
g
es
in
ac
ce
s
s
in
g
p
r
o
p
er
tr
ea
tm
en
t
;
ii)
Fu
r
th
er
m
o
r
e
,
th
e
s
tu
d
y
h
i
g
h
l
ig
h
ts
th
e
im
p
o
r
tan
ce
o
f
ea
r
l
y
d
etec
tio
n
in
im
p
r
o
v
in
g
p
a
tien
t
o
u
tco
m
es,
in
g
en
er
al
;
iii)
An
in
teg
r
ate
d
m
et
h
o
d
f
o
r
d
ete
ctin
g
lu
n
g
ca
n
ce
r
v
ia
C
T
s
ca
n
n
in
g
v
ia
o
p
tim
izatio
n
,
d
ee
p
lear
n
in
g
,
an
d
I
o
T
d
ata
tr
an
s
m
is
s
io
n
;
iv
)
Hig
h
-
ac
cu
r
ac
y
lu
n
g
d
is
ea
s
e
class
if
icatio
n
v
ia
lo
g
is
tic
r
eg
r
ess
io
n
an
d
ad
v
an
ce
d
f
ea
tu
r
e
e
x
tr
ac
tio
n
tech
n
iq
u
es
.
I
n
s
u
m
m
ar
y
,
th
e
o
n
g
o
i
n
g
r
esear
ch
ef
f
o
r
ts
in
L
u
n
g
ca
n
c
er
ar
e
cr
u
cial
f
o
r
d
ev
elo
p
in
g
b
etter
tr
ea
tm
en
t
s
tr
ateg
ies
an
d
en
h
an
cin
g
p
at
ien
t
ca
r
e.
B
ased
u
p
o
n
th
e
liter
atu
r
e
r
e
v
iew,
a
p
r
ec
lin
ical
m
o
lecu
le
is
s
till
to
b
e
id
en
tifie
d
,
f
o
c
u
s
in
g
o
n
L
ip
i
n
s
k
i
v
alu
es,
ex
ce
llen
t
d
o
c
k
in
g
s
co
r
e,
p
I
C
v
alu
es
to
ac
t h
as a
p
r
o
b
ab
le
m
o
lecu
le
in
to
th
e
ca
s
es f
o
r
l
u
n
g
ca
n
ce
r
.
T
ab
le
1
.
Su
m
m
a
r
y
o
f
lit
er
atu
r
e
S.
No
K
e
y
f
i
n
d
i
n
g
s
a
n
d
g
a
p
s
Met
h
o
d
o
l
o
g
y
/
a
p
p
r
o
ac
h
Ci
t
at
i
o
n
1
Id
e
n
t
i
f
i
c
at
i
o
n
o
f
ac
t
i
o
n
a
b
l
e
t
a
rg
et
s
i
s
e
s
s
en
t
i
al
fo
r
l
u
n
g
c
an
cer
d
r
u
g
d
i
s
co
v
e
ry
.
G
en
o
m
i
c
d
a
t
a
,
i
n
cl
u
d
i
n
g
t
h
e
Ca
n
ce
r
G
e
n
o
me
A
t
l
a
s
(
T
CG
A
)
a
n
d
G
e
n
o
mi
c
D
a
t
a
C
o
mm
o
n
s
(
G
D
C
)
,
h
a
v
e
b
ee
n
i
n
s
t
r
u
m
en
t
a
l
i
n
i
d
en
t
i
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y
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g
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e
y
d
r
i
v
er
m
u
t
at
i
o
n
s
a
n
d
p
at
h
w
a
y
s
.
Co
m
p
u
t
at
i
o
n
al
b
i
o
l
o
g
y
,
g
e
n
o
m
i
cs
,
b
i
o
i
n
f
o
rma
t
i
c
s
[1
]
2
V
i
rt
u
a
l
s
c
ree
n
i
n
g
i
s
a
cri
t
i
ca
l
s
t
e
p
i
n
s
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l
i
c
o
d
r
u
g
d
i
s
c
o
v
er
y
,
e
n
a
b
l
i
n
g
t
h
e
eff
i
c
i
e
n
t
p
r
i
o
ri
t
i
za
t
i
o
n
o
f
co
mp
o
u
n
d
s
.
Mac
h
i
n
e
l
ear
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i
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g
a
l
g
o
ri
t
h
m
s
h
av
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rt
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s
cr
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g
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a
l
s
cree
n
i
n
g
,
mac
h
i
n
e
l
ear
n
i
n
g
[2
]
3
T
a
r
g
e
t
e
d
t
h
e
r
a
p
i
e
s
f
o
r
l
u
n
g
c
a
n
c
e
r
,
a
l
i
k
e
e
p
i
d
erma
l
g
r
o
w
t
h
fac
t
o
r
rece
p
t
o
r
(
E
G
F
R
)
a
n
d
a
n
a
p
l
a
s
t
i
c
l
y
m
p
h
o
m
a
k
i
n
a
s
e
(
A
L
K
)
i
n
h
i
b
i
t
o
r
s
,
h
a
v
e
b
e
e
n
d
e
v
e
l
o
p
e
d
b
a
s
e
d
o
n
a
c
t
i
o
n
a
b
l
e
t
a
r
g
e
t
s
i
d
e
n
t
i
f
i
e
d
u
s
i
n
g
i
n
s
i
l
i
c
o
a
p
p
r
o
a
c
h
e
s
.
T
ar
g
e
t
i
d
en
t
i
f
i
ca
t
i
o
n
,
d
r
u
g
d
e
s
i
g
n
[3
]
4
Mo
l
ec
u
l
ar
d
o
c
k
i
n
g
i
mi
t
a
t
i
o
n
s
s
h
o
w
a
cr
u
c
i
a
l
r
o
l
e
i
n
p
re
d
i
ct
i
n
g
d
r
u
g
-
t
a
rg
et
i
n
t
era
ct
i
o
n
s
.
A
d
v
an
ce
d
d
o
ck
i
n
g
p
r
o
ce
d
u
re
s
,
s
u
c
h
as
A
u
t
o
D
o
c
k
V
i
n
a
,
h
a
v
e
c
o
n
t
r
i
b
u
t
e
d
t
o
t
h
e
d
i
s
c
o
v
er
y
o
f
p
o
t
e
n
t
i
al
l
u
n
g
ca
n
c
er
d
r
u
g
c
an
d
i
d
at
es
.
Mo
l
ec
u
l
ar
d
o
ck
i
n
g
,
co
m
p
u
t
at
i
o
n
al
s
i
m
u
l
a
t
i
o
n
s
[4
]
5
In
s
i
l
i
c
o
d
r
u
g
d
i
s
c
o
v
er
y
h
a
s
t
h
e
p
r
o
b
a
b
l
e
t
o
r
u
s
h
t
h
e
i
d
e
n
t
i
f
i
c
at
i
o
n
fo
r
i
n
n
o
v
a
t
i
v
e
l
u
n
g
c
an
ce
r
d
r
u
g
c
an
d
i
d
at
es
,
p
l
u
mme
t
i
n
g
t
i
me
an
d
co
s
t
.
A
d
v
a
n
c
es
i
n
c
o
m
p
u
t
at
i
o
n
al
t
o
o
l
s
a
n
d
d
a
t
a
i
n
t
e
g
ra
t
i
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are
s
h
a
p
i
n
g
t
h
e
f
u
t
u
re
o
f
t
h
e
fi
e
l
d
.
In
s
i
l
i
c
o
d
r
u
g
d
i
s
c
o
v
ery
,
d
a
t
a
i
n
t
eg
r
at
i
o
n
[5
]
Evaluation Warning : The document was created with Spire.PDF for Python.
I
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I
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3
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Sep
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25
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1306
2.
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[
1
]
–
[
5
]
.
I
n
t
h
e
n
e
x
t
s
t
e
p
,
a
n
u
m
b
e
r
o
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m
o
l
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u
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h
a
v
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l
i
s
t
e
d
o
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t
t
h
o
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a
n
n
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u
t
r
a
l
i
z
e
t
h
e
t
a
r
g
e
t
(
A
c
i
d
i
c
m
a
m
m
a
l
i
a
n
c
h
i
t
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n
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e
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o
t
e
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n
)
.
F
o
u
n
d
e
d
o
n
t
o
t
h
e
I
C
5
0
p
r
i
n
c
i
p
l
e
s
,
a
l
l
t
h
e
m
o
l
e
c
u
l
e
s
w
e
r
e
c
o
n
s
i
d
e
r
e
d
i
n
t
o
t
h
r
e
e
c
a
t
e
g
o
r
i
e
s
:
a
c
t
i
v
e
,
i
n
t
e
r
m
e
d
i
a
t
e
a
n
d
i
n
a
c
t
i
v
e
m
o
l
e
c
u
l
e
s
.
T
h
e
f
o
llo
win
g
m
eth
o
d
o
lo
g
ical
ap
p
r
o
ac
h
h
as b
ee
n
u
s
ed
:
i)
I
d
en
tific
atio
n
a
n
d
v
alid
atio
n
o
f
tar
g
ets
:
C
h
o
o
s
in
g
an
d
co
n
f
ir
m
in
g
a
g
o
o
d
th
er
a
p
eu
tic
tar
g
et
is
th
e
f
ir
s
t
s
tag
e
in
to
th
e
d
r
u
g
d
etec
tio
n
p
r
o
ce
s
s
.
Po
ten
tial
tar
g
ets
f
o
r
lu
n
g
ca
n
ce
r
co
u
l
d
b
e
p
ar
ti
cu
lar
p
r
o
tein
s
,
r
ec
ep
to
r
s
,
o
r
g
en
etic
ab
n
o
r
m
alities
th
at
ar
e
in
v
o
lv
ed
in
th
e
d
ev
elo
p
m
e
n
t
an
d
s
p
r
ea
d
o
f
th
e
tu
m
o
r
.
I
n
s
ilico
s
tr
ateg
ies
a
lo
n
g
with
d
a
ta
m
in
in
g
,
b
io
i
n
f
o
r
m
atics,
an
d
g
en
o
m
ics
ev
alu
atio
n
ar
e
u
s
ed
to
d
is
co
v
er
an
d
v
alid
ate
th
o
s
e
tar
g
ets.
T
h
is
lev
el
d
eter
m
in
es
wh
eth
er
o
r
n
o
t
th
e
c
h
o
s
en
g
o
al
i
s
b
io
lo
g
ically
s
u
b
s
tan
tial
an
d
co
n
tr
ib
u
tes
s
u
b
s
tan
tially
to
th
e
s
ick
n
ess
.
F
i
n
d
in
g
a
s
u
cc
ess
r
em
ed
y
alter
n
ativ
e
ca
lls
f
o
r
an
in
f
o
r
m
atio
n
o
f
way
s
p
r
o
tein
s
,
g
en
etic
in
f
o
r
m
atio
n
,
an
d
d
i
s
ea
s
e
d
ev
elo
p
m
en
t in
ter
ac
t.
ii)
Pre
-
s
cr
ee
n
in
g
:
C
h
em
ical
c
o
m
p
o
u
n
d
s
in
m
ass
iv
e
m
o
lecu
lar
lib
r
ar
ies
ar
e
lo
o
k
ed
af
ter
an
d
r
an
k
ed
th
e
u
s
e
o
f
a
co
m
p
u
tatio
n
al
tech
n
iq
u
e
ca
lled
v
ir
tu
al
s
cr
ee
n
in
g
.
T
h
is
s
eg
m
en
t
o
f
th
e
lu
n
g
ca
n
ce
r
d
r
u
g
d
is
co
v
er
y
p
r
o
ce
d
u
r
e
c
o
n
s
is
ts
o
f
s
ea
r
ch
i
n
g
th
r
o
u
g
h
c
h
em
ical
d
atab
as
es
f
o
r
ca
p
ab
ilit
y
tr
ea
tm
en
t
al
ter
n
ativ
es
th
at
wo
u
ld
en
g
a
g
e
with
th
e
s
elec
ted
g
o
al.
Vir
tu
al
s
cr
ee
n
in
g
s
tr
ateg
ies
b
ased
o
n
s
h
ap
e
an
d
m
o
lecu
la
r
m
o
d
elin
g
ar
e
u
s
ed
to
ev
al
u
at
e
a
co
m
p
o
u
n
d
`
s
b
in
d
in
g
af
f
i
n
ities
with
tar
g
et
p
r
o
tein
s
.
T
h
e
ac
cu
r
ac
y
o
f
m
o
lecu
lar
in
ter
ac
tio
n
s
an
d
p
r
e
d
ictiv
e
m
o
d
elin
g
ar
e
cr
itical
to
th
is
p
r
o
ce
d
u
r
e'
s
s
u
cc
ess
.
iii)
P
h
a
r
m
a
c
o
k
i
n
e
t
ic
ev
a
l
u
at
i
o
n
:
Un
d
e
r
s
t
a
n
d
i
n
g
t
h
e
p
h
a
r
m
a
c
o
k
i
n
e
t
i
c
c
h
a
r
a
c
t
e
r
is
ti
c
s
o
f
t
h
e
r
a
p
e
u
t
i
c
a
p
p
li
c
a
n
ts
,
i
n
c
l
u
s
i
v
e
o
f
a
b
s
o
r
p
t
i
o
n
,
d
i
s
t
r
i
b
u
t
i
o
n
,
m
e
t
a
b
o
l
is
m
,
a
n
d
e
x
c
r
e
t
io
n
(
A
D
M
E
)
,
h
a
s
a
es
s
e
n
t
i
a
l
p
h
a
s
e
i
n
t
h
e
d
r
u
g
i
m
p
r
o
v
e
m
e
n
t
p
r
o
g
r
e
s
s
i
o
n
.
W
h
e
n
a
s
s
e
s
s
i
n
g
t
h
e
p
h
a
r
m
a
c
o
k
i
n
e
t
i
c
r
es
i
d
e
n
c
es
o
f
v
i
a
b
le
t
h
e
r
ap
e
u
t
i
c
d
r
u
g
s
,
p
r
e
d
i
c
t
i
v
e
s
t
r
a
te
g
i
es
a
n
d
i
n
s
il
ic
o
m
o
d
e
l
s
a
r
e
es
s
e
n
ti
a
l
.
T
h
e
e
f
f
i
c
a
c
y
o
f
t
h
e
s
c
ie
n
t
i
f
ic
t
r
ia
l
s
m
a
y
b
e
e
x
p
e
c
t
e
d
v
i
a
w
a
y
o
f
m
e
a
n
s
o
f
d
e
c
i
d
i
n
g
o
n
d
r
u
g
a
p
p
l
i
c
a
n
t
s
w
it
h
f
a
v
o
r
a
b
le
p
h
a
r
m
a
c
o
k
i
n
e
t
i
c
p
r
o
p
e
r
t
i
es
.
iv
)
Do
ck
in
g
o
f
m
o
lec
u
les:
Mo
lecu
lar
d
o
c
k
in
g
is
a
im
p
o
r
tan
t
le
v
el
in
t
h
e
in
s
ilico
d
r
u
g
d
is
co
v
er
y
p
r
o
ce
s
s
.
Mo
d
elin
g
th
e
in
ter
p
la
y
am
o
n
g
th
e
d
r
u
g
ca
n
d
id
ate
an
d
th
e
t
ar
g
et
p
r
o
tein
was
ess
en
tial
to
ar
e
ex
p
ec
tin
g
b
in
d
in
g
a
f
f
in
ities
,
m
ec
h
an
is
m
s
o
f
b
in
d
in
g
,
an
d
ca
p
ac
ity
d
r
u
g
-
p
r
o
tein
in
ter
ac
tio
n
s
.
Mo
le
cu
lar
d
o
ck
i
n
g
in
v
esti
g
atio
n
s
a
r
e
co
n
d
u
cted
u
s
in
g
v
ar
io
u
s
tec
h
n
iq
u
es
a
n
d
s
o
f
twar
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to
o
ls
,
to
ascer
tain
th
e
m
o
s
t
s
u
itab
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d
r
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g
ca
n
d
id
ates
f
o
r
f
u
r
th
e
r
d
ev
elo
p
m
en
t.
Valid
atio
n
o
f
th
e
in
ter
ac
tio
n
s
b
etwe
en
th
e
d
r
u
g
an
d
tar
g
e
t
p
r
o
tein
s
is
cr
u
cial
f
o
r
th
e
s
u
cc
ess
o
f
th
er
ap
eu
tic
in
ter
v
en
tio
n
s
.
v)
C
u
r
r
en
t
p
r
o
g
r
ess
an
d
d
if
f
ic
u
lties
:
T
h
is
p
ap
er
r
ev
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t
h
e
cu
r
r
en
t
p
r
o
g
r
ess
in
s
ilico
lu
n
g
ca
n
ce
r
d
r
u
g
d
is
co
v
er
y
,
f
o
c
u
s
in
g
o
n
t
h
e
l
atest
p
r
o
g
r
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io
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s
in
to
ar
tific
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in
tellig
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ce
th
e
n
m
ac
h
in
e
lear
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in
g
f
o
r
p
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ed
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m
o
d
ellin
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d
itio
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ally
,
th
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tu
d
y
o
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ein
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lig
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d
in
te
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s
u
s
in
g
m
o
lec
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lar
d
y
n
am
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s
s
im
u
latio
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s
p
r
o
v
id
es
v
alu
ab
le
ac
u
m
en
s
in
to
th
e
m
ac
h
in
er
ie
s
o
f
d
ee
d
o
f
p
o
te
n
tial
d
r
u
g
s
.
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h
e
in
teg
r
atio
n
o
f
s
tr
u
ctu
r
al
b
io
lo
g
y
d
ata
in
to
d
r
u
g
d
esig
n
h
as
ac
ce
ler
ated
th
e
d
r
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d
is
co
v
e
r
y
p
r
o
ce
s
s
f
o
r
lu
n
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ca
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ce
r
,
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ch
allen
g
es
in
o
b
tain
in
g
ac
cu
r
ate
p
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ed
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m
o
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els.
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all,
th
e
in
teg
r
atio
n
o
f
ad
v
a
n
ce
d
co
m
p
u
tatio
n
al
m
eth
o
d
s
with
b
io
lo
g
ical
in
s
ig
h
ts
h
o
ld
s
p
r
o
m
is
e
f
o
r
th
e
co
n
tin
u
ed
ad
v
an
ce
m
en
t
o
f
lu
n
g
ca
n
ce
r
d
r
u
g
d
is
co
v
er
y
ef
f
o
r
ts
.
T
h
e
co
n
f
ir
m
atio
n
o
f
co
m
p
u
ter
p
r
ed
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n
s
th
r
o
u
g
h
ex
p
e
r
im
e
n
tal
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esear
ch
,
th
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r
eq
u
ir
e
m
en
t
f
o
r
p
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ec
is
e
an
d
tr
u
s
two
r
th
y
d
atasets
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an
d
th
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eth
ical
is
s
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es
s
u
r
r
o
u
n
d
in
g
th
e
u
s
e
o
f
p
atien
t d
ata
ar
e
s
o
m
e
o
f
th
e
ch
allen
g
es.
v
i
)
F
u
t
u
r
e
e
x
p
e
c
t
a
t
i
o
n
s
:
L
u
n
g
c
a
n
c
e
r
i
n
s
i
l
i
c
o
d
r
u
g
d
i
s
c
o
v
e
r
y
h
a
s
a
l
o
t
o
f
p
o
t
e
n
t
i
a
l
,
a
n
d
m
o
r
e
r
e
s
e
a
r
c
h
s
h
o
u
l
d
i
m
p
r
o
v
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t
h
e
p
r
o
c
e
s
s
'
s
a
c
c
u
r
a
cy
a
n
d
e
f
f
i
c
i
e
n
c
y
.
P
r
o
s
p
e
c
ts
f
o
r
t
h
e
f
u
t
u
r
e
i
n
c
l
u
d
e
i
n
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ti
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m
u
l
t
i
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o
m
i
cs
d
a
t
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t
o
f
i
n
d
n
o
v
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l
t
a
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g
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ts
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n
d
th
e
r
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p
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t
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c
c
a
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d
i
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te
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d
e
v
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l
o
p
in
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m
o
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p
r
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s
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p
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ti
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m
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l
s
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a
n
d
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p
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d
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y
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i
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b
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c
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d
-
b
a
s
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d
r
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o
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s
.
3.
RE
SU
L
T
S AN
D
D
I
SCU
SS
I
O
N
C
h
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MBL
d
atab
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is
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ap
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API
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f
th
is
web
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s
ito
r
y
h
as
b
ee
n
u
s
ed
with
Py
th
o
n
t
o
ex
tr
ac
t
p
r
o
tein
s
ass
o
ciate
d
in
th
e
lu
n
g
ca
n
ce
r
.
Acid
ic
m
am
m
alian
ch
itin
ase,
C
h
e
MBL
id
:
C
HE
MBL1
2
9
3
1
9
7
is
id
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tifie
d
as
a
tar
g
et
p
r
o
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f
o
r
f
u
r
th
er
s
tu
d
y
to
o
v
er
co
m
e
lu
n
g
ca
n
ce
r
.
I
n
th
e
n
e
x
t
s
tep
,
s
ev
er
al
m
o
lecu
les
h
av
e
b
ee
n
lis
ted
th
at
ca
n
n
e
u
tr
alize
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m
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alian
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itin
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ased
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2
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8
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eq
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t.
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h
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r
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d
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at
ac
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ac
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ly
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wo
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wh
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g
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r
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is
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el
p
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k
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I
n
F
i
g
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1
(
a
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,
s
h
o
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t
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m
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d
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M
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tl
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m
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s
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(
a)
(
b
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c)
(
d
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Fig
u
r
e
1
.
Data
s
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ter
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o
f
m
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[
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Co
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a
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v
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rs
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c
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g
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n
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x
p
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Kh
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n
h
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s
m
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sig
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ro
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K
h
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CIE,
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