I
nte
rna
t
io
na
l J
o
urna
l o
f
Adv
a
nces in Applie
d Science
s
(
I
J
AAS)
Vo
l.
3
,
No
.
3
,
Sep
tem
b
er
201
4
,
p
p
.
15
1
~
15
7
I
SS
N:
2252
-
8814
151
J
o
ur
na
l ho
m
ep
a
g
e
:
h
ttp
:
//ia
e
s
jo
u
r
n
a
l.c
o
m/o
n
lin
e/in
d
ex
.
p
h
p
/I
J
AAS
Ins
ilico
Identi
ficatio
n of P
o
tent
Inh
ibitor fro
m
Andr
o
g
ra
phis
Panicula
ta f
o
r
E
S
BL
s
Ay
s
ha
O
.
S
*
,
M
u
m
t
a
j
P
ee
r
M
o
ha
m
m
e
d
**,
Dha
m
o
t
ha
ra
n
R*
*
*
*
P
G
&
Re
s
e
a
rc
h
De
p
a
rt
m
e
n
t
o
f
M
icro
b
i
o
l
o
g
y
,
M
o
h
a
m
e
d
S
a
th
a
k
Co
ll
e
g
e
o
f
A
rts
&
S
c
ien
c
e
,
In
d
ia
**
De
p
a
rt
m
e
n
t
o
f
Bio
in
f
o
rm
a
ti
c
s
,
M
o
h
a
m
e
d
S
a
th
a
k
Co
ll
e
g
e
o
f
A
rt
s &
S
c
ien
c
e
,
In
d
ia
*
*
*
P
G
&
Re
s
e
a
rc
h
De
p
a
rt
m
e
n
t
o
f
P
lan
t
Bio
lo
g
y
&
Bio
tec
h
n
o
l
o
g
y
,
P
re
sid
e
n
c
y
Co
ll
e
g
e
,
In
d
ia
Art
icle
I
nfo
AB
ST
RAC
T
A
r
ticle
his
to
r
y:
R
ec
eiv
ed
J
u
n
11
,
2
0
1
4
R
ev
i
s
ed
A
u
g
14
,
2
0
1
4
A
cc
ep
ted
A
u
g
2
4
,
2
0
1
4
T
h
e
stu
d
y
a
i
m
e
d
a
t
d
o
c
k
in
g
o
f
T
EM
-
5
2
&
m
o
d
e
led
CT
X
–
M
-
1
3
b
y
e
th
a
n
o
l
e
x
trac
ted
c
o
m
p
o
u
n
d
s
f
ro
m
An
d
ro
g
ra
p
h
is
p
a
n
icu
la
ta
a
n
d
to
p
re
d
ict
th
e
ir
b
i
n
d
i
n
g
e
ff
icie
n
c
y
.
BLAS
T
-
P
w
a
s
p
e
r
f
o
r
m
e
d
to
re
tri
e
v
e
su
it
a
b
le
tem
p
late
s
f
o
r
h
o
m
o
lo
g
y
-
m
o
d
e
li
n
g
u
sin
g
th
e
b
la
CT
X
-
M
se
q
u
e
n
c
e
s
o
b
tain
e
d
f
ro
m
G
e
n
b
a
n
k
.
P
ro
tei
n
Da
ta
Ba
n
k
(P
DB)
IDs
o
f
th
e
se
tem
p
late
s
we
re
re
tri
e
v
e
d
.
M
o
d
e
ls
w
e
re
p
re
p
a
re
d
u
sin
g
S
w
iss
-
M
o
d
e
l
-
S
e
rv
e
r
a
n
d
v
e
ri
f
ied
b
y
P
r
o
c
h
e
c
k
a
n
d
3
D
p
r
o
g
ra
m
m
e
s
RA
M
P
AG
E
w
a
s
u
se
d
to
p
re
p
a
re
Ra
m
a
c
h
a
n
d
ra
n
p
lo
ts.
T
h
e
1
3
-
He
x
y
l
-
o
x
a
-
c
y
c
lo
tri
d
e
c
-
10
-
En
-
2
-
o
n
e
w
a
s
se
lec
t
e
d
a
s
li
g
a
n
d
f
o
r
th
is
d
o
c
k
in
g
stu
d
y
f
ro
m
th
e
d
a
ta
g
e
n
e
ra
ted
b
y
M
a
ss
sp
e
c
tro
m
e
tr
y
a
n
a
l
y
sis
o
f
m
e
th
a
n
o
l
e
x
trac
ted
c
o
m
p
o
u
n
d
s
f
ro
m
An
d
ro
g
ra
p
h
is
p
a
n
icu
l
a
ta
.
T
h
e
stru
c
tu
re
w
a
s
d
ra
w
n
m
a
n
u
a
ll
y
with
a
id
o
f
JME
a
n
d
it
s
d
ru
g
li
k
e
li
n
e
ss
&
m
o
lec
u
lar
p
r
o
p
e
rti
e
s
w
a
s
c
a
lcu
late
d
u
si
n
g
P
re
A
d
m
e
t
se
rv
e
r.
Do
c
k
in
g
wa
s
p
e
r
f
o
r
m
e
d
b
y
u
sin
g
d
o
c
k
in
g
se
rv
e
r.
S
in
c
e
th
e
d
o
c
k
in
g
re
su
lt
s
p
ro
v
e
d
t
h
a
t
th
e
a
m
in
o
a
c
id
re
sid
u
e
s
S
e
r7
0
,
S
e
r
1
3
0
,
S
e
r2
3
7
,
A
rg
2
7
6
a
n
d
T
h
r2
3
5
o
f
CT
X
-
M
-
1
3
(e
n
z
y
m
e
)
m
a
k
e
im
p
o
rtan
t
c
o
n
tac
ts
w
it
h
th
e
li
g
a
n
d
,
re
se
a
rc
h
e
rs
a
re
e
x
p
e
c
ted
to
d
u
ly
u
ti
li
z
e
th
is
in
f
o
rm
a
ti
o
n
f
o
r
d
e
sig
n
in
g
m
o
re
p
o
ten
t
a
n
d
CT
X
-
M
i
n
h
ib
it
o
rs.
K
ey
w
o
r
d
:
An
d
r
o
g
r
ap
h
is
p
an
icu
la
ta
C
T
X
-
M
-
13
13
-
Hex
y
l
-
o
x
a
-
c
y
clo
tr
id
ec
-
10
-
En
-
2
-
o
n
e
L
i
g
an
d
T
E
M
-
52
Co
p
y
rig
h
t
©
201
4
In
s
t
it
u
te o
f
A
d
v
a
n
c
e
d
E
n
g
i
n
e
e
rin
g
a
n
d
S
c
ien
c
e
.
Al
l
rig
h
ts
re
se
rv
e
d
.
C
o
r
r
e
s
p
o
nd
ing
A
uth
o
r
:
Ay
s
h
a
O.
S
,
P
G
&
R
esear
ch
Dep
ar
t
m
en
t o
f
Mic
r
o
b
io
lo
g
y
,
Mo
h
a
m
ed
Sat
h
a
k
C
o
lle
g
e
o
f
A
r
t
s
&
Sc
ien
ce
,
Sh
o
li
n
g
a
n
all
u
r
,
C
h
en
n
ai
-
6
0
0
1
1
9
,
I
n
d
ia
.
E
m
ail:
a
y
s
h
a
m
o
h
a
m
ed
7
8
6
@
g
m
ail.
co
m
1.
I
NT
RO
D
UCT
I
O
N
E
m
er
g
i
n
g
r
esis
ta
n
t
b
ac
ter
ial
s
tr
ain
s
ar
e
t
h
e
m
o
s
t
s
er
io
u
s
g
lo
b
al
th
r
ea
ts
to
tr
ea
t
m
e
n
t
to
t
h
e
in
f
ec
tio
u
s
d
is
ea
s
es.
W
h
ile
in
1
9
7
5
j
u
s
t
3
%
o
f
r
esis
tan
ce
is
o
late
s
w
er
e
r
eg
is
ter
ed
b
y
2
0
0
3
it
h
ad
g
r
o
w
n
to
5
9
.
5
%.
Mo
r
e
p
eo
p
le
h
av
e
d
ied
o
f
th
e
b
ac
ter
ial
in
f
ec
tio
n
ca
u
s
ed
b
y
v
a
r
io
u
s
m
icr
o
b
es
r
ath
er
th
a
n
HI
V.
T
h
e
r
esis
tan
t
o
r
g
an
is
m
s
ar
e
n
o
w
a
w
o
r
ld
w
id
e
p
r
o
b
le
m
.
T
h
e
w
id
e
s
p
r
ea
d
u
s
e
o
f
a
n
tib
io
tic
s
i
n
h
o
s
p
itals
h
a
s
led
to
e
m
er
g
e
n
ce
o
f
m
u
ltid
r
u
g
r
es
is
tan
t
o
r
g
a
n
is
m
s
o
f
lo
w
v
ir
u
le
n
ce
li
k
e
K
leb
s
iella
ca
u
s
i
n
g
s
er
io
u
s
o
p
p
o
r
tu
n
is
t
ic
in
f
ec
tio
n
s
.
T
h
e
r
esis
tan
t
s
tr
ai
n
s
ca
n
b
e
f
o
u
n
d
in
a
v
ar
ie
t
y
o
f
E
n
ter
o
b
ater
iace
ae
s
p
ec
ies;
h
o
w
e
v
er
t
h
e
m
aj
o
r
ity
o
f
m
u
l
ti
-
d
r
u
g
r
esis
ta
n
t
s
tr
ai
n
s
ar
e
K
.
p
n
eu
mo
n
ia
e,
K
.
o
xy
to
c
a
an
d
E
s
ch
erich
ia
co
li
.
Am
o
n
g
th
e
s
e
v
er
al
d
r
u
g
r
esis
ta
n
t
b
ac
ter
ia
β
-
lac
ta
m
a
s
e
p
r
o
d
u
ctio
n
is
th
e
m
o
s
t
i
m
p
o
r
tan
t
m
ec
h
a
n
is
m
o
f
r
es
is
ta
n
c
e
to
p
en
icillin
a
n
d
ce
p
h
alo
s
p
o
r
in
s
.
T
h
e
m
ec
h
a
n
i
s
m
o
f
r
esi
s
ta
n
ce
w
as
th
e
p
r
o
d
u
ctio
n
o
f
E
x
te
n
d
ed
Sp
ec
tr
u
m
o
f
β
-
L
ac
ta
m
ase
s
(
E
SB
L
s
)
.
T
h
e
an
tib
io
tic
r
esi
s
t
an
ce
is
co
n
f
er
r
ed
b
y
s
e
v
er
al
m
ec
h
an
i
s
m
s
i
n
b
ac
ter
ia.
T
h
e
m
o
s
t
co
m
m
o
n
m
o
d
e
o
f
r
esi
s
tan
ce
is
en
z
y
m
atic
in
a
ctiv
atio
n
o
f
t
h
e
a
n
tib
io
tic.
W
h
en
t
h
e
e
n
z
y
m
e
is
m
o
d
i
f
ied
it
w
ill
n
o
t
a
f
f
ec
t
th
e
m
icr
o
o
r
g
an
i
s
m
.
(
T
o
d
ar
,
2
0
0
8
)
.
T
h
e
o
th
er
m
ec
h
a
n
i
s
m
is
b
y
a
lter
atio
n
o
f
an
tib
io
tic
tar
g
et
s
it
e.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
SS
N
:
2
2
5
2
-
8814
IJ
AA
S
Vo
l.
3
,
No
.
3
,
Sep
tem
b
er
2
0
1
4
:
15
1
–
15
7
152
1
.
1
.
β
-
L
a
ct
a
m
a
s
es
β
-
lacta
m
a
s
es
ar
e
en
z
y
m
es
p
r
o
d
u
ce
d
b
y
s
o
m
e
b
ac
ter
ia
an
d
ar
e
r
esp
o
n
s
ib
le
f
o
r
th
eir
r
esis
ta
n
ce
to
b
eta
-
lacta
m
an
tib
io
tics
li
k
e
p
en
icilli
n
s
,
ce
p
h
a
lo
s
p
o
r
in
s
(
ar
e
r
elativ
el
y
r
e
s
is
ta
n
t
t
o
b
eta
lacta
m
ase)
,
ce
p
h
a
m
y
ci
n
s
an
d
ca
r
b
ap
en
em
s
(
er
tap
en
e
m
)
.
T
h
ese
an
t
ib
io
tics
h
av
e
a
co
m
m
o
n
ele
m
e
n
t
in
th
e
ir
m
o
lecu
la
r
s
tr
u
ct
u
r
e:
a
f
o
u
r
ato
m
r
in
g
k
n
o
w
n
as
a
b
eta
-
lac
ta
m
.
T
h
e
lacta
m
a
s
e
en
z
y
m
e
b
r
ea
k
s
th
e
r
i
n
g
o
p
en
an
d
d
ea
ctiv
ates
t
h
e
m
o
lecu
le
‟
s
an
tib
ac
ter
ial
p
r
o
p
er
ties
.
T
h
e
m
ec
h
a
n
is
m
o
f
ac
tio
n
o
f
β
-
l
ac
ta
m
ase
s
i
n
cl
u
d
es
attac
k
s
o
n
a
m
id
e
b
o
n
d
i
n
t
h
e
β
-
lacta
m
r
i
n
g
o
f
p
en
c
illi
n
an
d
ce
p
h
alo
s
p
o
r
in
to
p
r
o
d
u
ce
p
en
cilli
n
o
ic
ac
id
an
d
ce
p
h
alo
s
p
o
r
ic
ac
id
r
esp
ec
tiv
ely
,
u
lti
m
ate
l
y
r
e
n
d
er
in
g
t
h
e
co
m
p
o
u
n
d
in
ac
ti
v
e
(
P
h
ilip
p
o
n
et
a
l
.
,
1
9
8
9
)
.
1
.
2
.
E
x
t
en
ded S
pect
ru
m
o
f
β
-
L
a
ct
a
m
a
s
es
(
E
SB
L
s
)
E
x
ten
d
ed
Sp
ec
tr
u
m
B
eta
L
ac
t
a
m
ase
s
(
E
SB
L
s
)
h
av
e
b
ec
o
m
e
a
ch
al
len
g
e
b
o
th
f
r
o
m
t
h
e
d
ia
g
n
o
s
tic
as
w
ell
as
o
n
th
e
m
a
n
a
g
e
m
en
t
p
o
in
t
o
f
v
ie
w
.
(
Mir
za
et
a
l.,
2
0
0
6
)
.
T
h
e
f
ir
s
t
E
x
te
n
d
ed
-
s
p
ec
tr
u
m
β
-
lacta
m
ase
is
o
lates
w
er
e
d
is
co
v
er
ed
in
W
ester
n
E
u
r
o
p
e
in
th
e
m
id
1
9
8
0
‟
s
an
d
s
u
b
s
eq
u
en
tl
y
i
n
US
in
th
e
late
1
9
8
0
s
(
Nath
is
u
w
a
n
et
a
l
.
,
2
0
0
1
)
.
T
h
e
y
ca
n
b
e
f
o
u
n
d
i
n
a
w
id
e
v
ar
iet
y
o
f
E
n
ter
o
b
ac
ter
iace
ae
s
p
ec
ies
h
o
w
e
v
er
,
th
e
m
aj
o
r
ity
o
f
E
SB
L
p
r
o
d
u
cin
g
s
tr
ain
s
ar
e
K
leb
s
iel
la
p
n
eu
mo
n
ia
e
,
K
leb
s
iella
o
xy
to
ca
an
d
l
ater
in
E
s
ch
erich
ia
co
li
,
P
s
eu
d
o
mo
n
a
s
a
eru
g
i
n
o
s
a
an
d
S
err
a
tia
ma
r
ce
s
ce
n
s
an
d
o
th
er
g
r
a
m
-
n
eg
at
iv
e
b
ac
il
li
(
Kir
atis
in
et
a
l
.,
2
0
0
8
:
C
h
en
g
et
a
l
.
,
2
0
0
8
an
d
Mo
r
r
is
et
a
l
.
,
2
0
0
3
)
.
E
SB
L
s
ar
e
also
ab
le
to
h
y
d
r
o
l
y
ze
3
rd
an
d
4
th
g
en
er
atio
n
ce
p
h
alo
s
p
o
r
in
s
an
d
m
o
n
o
b
a
cta
m
s
.
E
SB
L
p
r
o
d
u
c
in
g
s
tr
ain
s
ar
e
i
n
h
ib
ited
b
y
β
-
lac
ta
m
ase
i
n
h
ib
ito
r
s
(
C
lav
u
la
n
ic
ac
id
,
S
u
lb
ac
ta
m
an
d
tazo
b
ac
ta
m
)
(
B
r
ad
f
o
r
d
,
2
0
0
1
:
P
ito
u
t
et
a
l.,
2
0
0
7
an
d
B
ali
et
a
l
,
2
0
1
0
)
.
T
r
ea
tm
en
t
o
f
i
n
f
ec
tio
n
s
ca
u
s
e
d
b
y
t
h
ese
r
e
s
is
ta
n
t
b
ac
ter
ia
h
as
b
ec
o
m
e
v
er
y
d
if
f
ic
u
lt
s
i
n
ce
th
e
y
ar
e
r
esis
ta
n
t
to
m
an
y
a
n
tib
io
tics
.
T
h
i
s
li
m
it
s
th
er
ap
eu
tic
o
p
tio
n
s
.
E
x
ten
d
ed
s
p
ec
tr
u
m
β
-
lacta
m
ases
ar
e
p
las
m
id
m
ed
iated
,
T
E
M
an
d
SHV
d
er
iv
ed
en
z
y
m
es,
m
o
s
t
co
m
m
o
n
l
y
f
o
u
n
d
i
n
K
leb
s
iella
s
p
p
.
,
f
o
llo
w
ed
b
y
E
s
ch
erich
ia
co
li
(
P
o
o
le,
2
0
0
4
)
.
Sin
g
le
a
m
i
n
o
ac
id
s
u
b
s
t
itu
t
io
n
s
at
p
o
s
itio
n
s
1
0
4
,
1
6
4
,
2
3
8
,
an
d
2
4
0
p
r
o
d
u
ce
th
e
E
SB
L
p
h
en
o
t
y
p
e,
b
u
t
E
SB
L
s
w
i
th
t
h
e
b
r
o
ad
est
s
p
ec
tr
u
m
u
s
u
all
y
h
av
e
m
o
r
e
t
h
an
a
s
i
n
g
le
a
m
i
n
o
ac
id
s
u
b
s
ti
tu
tio
n
.
B
ased
u
p
o
n
d
if
f
er
e
n
t c
o
m
b
i
n
a
tio
n
s
o
f
c
h
an
g
e
s
,
cu
r
r
en
tl
y
1
4
0
T
E
M
-
t
y
p
e
en
z
y
m
es
h
av
e
b
e
en
d
e
s
cr
ib
ed
.
Fig
u
r
e
1
.
P
r
o
ch
ec
k
an
al
y
s
is
r
e
s
u
lt
s
s
h
o
w
s
m
o
r
e
f
av
o
u
r
in
g
r
eg
io
n
s
ar
e
p
r
esen
t i
n
m
o
d
eled
p
r
o
tein
th
r
o
u
g
h
t
h
eir
R
a
m
ac
h
an
d
r
an
P
lo
t a
n
al
y
s
is
Fig
u
r
e
2
.
I
n
ter
ac
tio
n
o
f
1
3
Hex
y
l o
x
a
c
y
clo
tr
id
ec
1
0
–
en
–
2
-
On
e
&
T
E
M
52
Evaluation Warning : The document was created with Spire.PDF for Python.
IJ
AA
S
I
SS
N:
2252
-
8814
I
n
s
ilico
I
d
en
tifi
ca
tio
n
o
f P
o
ten
t I
n
h
ib
ito
r
fr
o
m
A
n
d
r
o
g
r
a
p
h
is
P
a
n
icu
la
ta
f
o
r
E
S
B
Ls
(
A
ysh
a
O.
S
)
153
Ma
n
y
β
-
lacta
m
a
s
e
g
en
e
s
h
a
v
e
b
ee
n
f
o
u
n
d
in
K
leb
s
iella
p
n
eu
mo
n
ia
e
p
lasm
id
s
i
n
cl
u
d
in
g
th
o
s
e
en
co
d
in
g
e
x
ten
d
ed
s
p
ec
tr
u
m
β
-
lacta
m
ases
(
E
SB
L
s
)
.
T
h
e
y
ar
e
e
n
co
d
ed
in
lar
g
e
p
la
s
m
i
d
s
w
it
h
s
izes
o
f
8
0
-
1
0
0
k
b
.
Me
m
b
er
s
o
f
th
e
f
a
m
i
l
y
E
n
tero
b
a
cteria
ce
a
e
co
m
m
o
n
l
y
ex
p
r
es
s
p
las
m
id
en
co
d
e
d
β
-
lacta
m
a
s
e
(
eg
)
T
E
M
-
1
,
T
E
M
-
2
an
d
SHV
-
1
)
w
h
ic
h
co
n
f
er
r
esis
tan
ce
to
p
en
icillin
s
b
u
t
n
o
t
to
ex
p
an
d
ed
s
p
ec
tr
u
m
o
f
ce
p
h
alo
s
p
o
r
in
s
.
I
n
th
e
m
id
1
9
8
0
s
a
n
e
w
g
r
o
u
p
o
f
en
z
y
m
e
s
,
th
e
ex
ten
d
ed
–
s
p
ec
tr
u
m
β
-
lacta
m
ase
s
(
E
SB
L
s
)
,
w
er
e
d
etec
ted
.
T
h
e
r
es
is
tan
ce
i
s
d
er
iv
ed
f
r
o
m
g
e
n
es
f
o
r
T
E
M
-
1
,
T
E
M
-
2
o
r
SHV
-
1
b
y
m
u
t
atio
n
s
t
h
at
a
lter
th
e
a
m
i
n
o
ac
id
co
n
f
i
g
u
r
atio
n
ar
o
u
n
d
th
e
ac
ti
v
e
s
ite
o
f
β
-
lact
a
m
ase
s
.
T
h
is
ex
te
n
d
s
t
h
e
s
p
ec
tr
u
m
o
f
β
-
lacta
m
an
tib
io
tics
s
u
s
ce
p
tib
le
to
h
y
d
r
o
ly
s
i
s
b
y
th
e
s
e
en
z
y
m
es.
C
ar
b
ap
en
e
m
s
ar
e
t
h
e
tr
ea
t
m
e
n
t
o
f
ch
o
ice
f
o
r
s
er
io
u
s
in
f
ec
tio
n
s
d
u
e
to
E
SB
L
p
r
o
d
u
cin
g
o
r
g
a
n
is
m
s
,
y
et
ca
r
b
ap
en
em
r
es
is
ta
n
t
i
s
o
lates
h
a
v
e
r
ec
e
n
tl
y
b
ee
n
r
ep
o
r
ted
.
Ho
w
e
v
er
,
tr
ea
t
m
e
n
t
w
it
h
s
u
c
h
an
tib
io
tics
h
a
s
b
ee
n
a
s
s
o
ciate
d
w
it
h
h
i
g
h
f
a
ilu
r
e
r
ate
s
i
n
r
e
ce
n
t
y
ea
r
s
C
T
X
-
M
e
x
ten
d
ed
-
s
p
ec
tr
u
m
β
-
lact
m
as
es
(
E
SB
L
s
)
h
av
e
v
er
y
r
ap
id
ly
d
is
s
e
m
i
n
ated
an
d
ar
e
n
o
w
f
r
eq
u
en
tl
y
r
ep
o
r
ted
f
r
o
m
co
u
n
tr
ies
a
ll
o
v
er
E
u
r
o
p
e
an
d
m
u
c
h
o
f
Asi
a.
(
Kap
il,
2
0
0
5
)
.
I
n
I
n
d
ia,
t
h
e
v
er
y
f
ir
s
t
r
ep
o
r
t
o
f
th
e
p
r
esen
ce
o
f
C
T
X
-
M
-
p
r
o
d
u
ci
n
g
E
n
ter
o
b
ac
ter
iace
ae
ca
m
e
f
r
o
m
Ne
w
Delh
i.
Six
s
tr
ai
n
s
i
s
o
lated
in
t
h
e
y
ea
r
2
0
0
0
w
er
e
in
v
esti
g
ated
,
all
th
e
s
tr
ain
s
w
er
e
f
o
u
n
d
to
b
e
u
n
r
elate
d
an
d
all
p
r
o
d
u
ce
d
C
T
X
-
M
-
1
5
.
Sin
ce
th
e
n
s
ev
er
al
I
n
d
ian
s
u
r
v
e
y
s
h
av
e
r
ep
o
r
ted
th
e
p
r
esen
ce
o
f
E
SB
L
s
in
c
lin
ical
is
o
late
s
b
ased
o
n
p
h
en
o
t
y
p
i
c
te
s
ts
.
R
ec
en
t
l
y
r
ep
o
r
ted
r
ates
v
ar
y
w
id
el
y
(
1
2
.
6
-
7
1
%),
w
it
h
m
o
s
t
s
tu
d
ie
s
r
ep
o
r
tin
g
p
r
ev
alen
ce
r
ate
o
f
ar
o
u
n
d
5
0
%
an
d
u
p
w
ar
d
s
.
C
o
n
s
id
er
i
n
g
a
p
o
p
u
latio
n
o
f
ap
p
r
o
x
i
m
atel
y
1
.
1
b
illi
o
n
in
I
n
d
ia,
it
r
ep
r
esen
t
s
a
v
er
y
lar
g
e
r
eser
v
o
ir
f
o
r
r
esis
ta
n
ce
g
e
n
e.
T
h
e
p
r
o
b
lem
o
f
e
m
er
g
i
n
g
b
ac
ter
ial
r
esis
ta
n
ce
tr
ad
itio
n
all
y
h
as
b
ee
n
s
o
lv
ed
b
y
t
h
e
d
is
co
v
er
y
o
f
n
e
w
an
ti
m
icr
o
b
ial
d
r
u
g
s
.
U
n
f
o
r
tu
n
atel
y
,
t
h
er
e
is
n
o
as
s
u
r
a
n
ce
t
h
at
t
h
e
d
ev
e
lo
p
m
en
t
o
f
n
e
w
a
n
tib
io
tics
ca
n
k
ee
p
p
ac
e
w
it
h
th
e
ab
ilit
y
o
f
b
ac
ter
i
al
p
ath
o
g
en
s
to
d
ev
elo
p
r
esis
t
an
ce
.
T
h
e
in
cr
ea
s
ed
u
s
e
o
f
an
t
ib
io
tics
en
co
u
r
a
g
es
th
e
e
m
er
g
e
n
ce
o
f
r
e
s
is
ta
n
t
s
tr
ain
s
o
f
b
ac
ter
ia.
T
h
er
e
ar
e
g
eo
g
r
ap
h
ic
v
ar
iatio
n
s
i
n
a
n
tib
io
tic
r
esis
ta
n
ce
d
ep
en
d
in
g
o
n
lo
ca
l p
r
escr
ib
in
g
tr
en
d
s
.
R
esi
s
ta
n
ce
o
f
b
ac
ter
ia
is
co
n
ti
n
u
i
n
g
to
i
n
cr
ea
s
e,
b
o
th
i
n
n
u
m
b
er
an
d
in
v
ar
iet
y
,
b
u
t
n
o
t
s
i
g
n
i
f
ican
tl
y
d
if
f
er
en
t
n
e
w
er
a
n
tib
io
tics
ar
e
y
et
a
v
ailab
le.
T
h
u
s
to
d
a
y
t
h
er
e
is
a
n
u
r
g
e
n
t
n
ee
d
f
o
r
n
e
w
a
n
tib
ac
ter
ial
d
r
u
g
s
d
u
e
to
f
a
s
t
m
u
l
tip
licatio
n
o
f
d
r
u
g
r
esi
s
ta
n
ce
b
ac
ter
ial
s
tr
ain
s
a
n
d
also
n
e
w
,
e
m
er
g
i
n
g
p
at
h
o
g
e
n
s
.
T
h
e
u
lti
m
ate
g
o
al
to
o
f
f
er
ap
p
r
o
p
r
iate
an
d
e
f
f
icie
n
t
a
n
ti
m
icr
o
b
ial
d
r
u
g
s
to
th
e
p
atien
t
i
s
th
r
o
u
g
h
co
n
ti
n
u
o
u
s
s
t
u
d
ies
to
d
ev
elo
p
n
e
w
d
r
u
g
s
,
ei
th
er
s
y
n
th
etic
o
r
n
atu
r
al.
Natu
r
al
p
r
o
d
u
cts,
ei
th
er
a
s
p
u
r
e
co
m
p
o
u
n
d
s
o
r
as
s
tan
d
ar
d
ized
p
lan
t e
x
tr
a
ct
p
r
o
v
id
e
u
n
li
m
ite
d
o
p
p
o
r
tu
n
itie
s
f
o
r
n
e
w
d
r
u
g
l
ea
d
s
b
ec
au
s
e
o
f
t
h
e
u
n
m
atc
h
ed
a
v
ailab
ilit
y
o
f
ch
e
m
ical
d
i
v
er
s
it
y
.
T
r
ad
itio
n
al
m
ed
icin
e
s
ar
e
u
s
ed
b
y
ab
o
u
t
6
0
p
er
ce
n
t
o
f
t
h
e
w
o
r
ld
‟
s
p
o
p
u
latio
n
.
T
h
ese
ar
e
u
s
ed
f
o
r
p
r
i
m
ar
y
h
ea
lt
h
ca
r
e
n
o
t
j
u
s
t
i
n
r
u
r
al
ar
ea
s
o
f
d
e
v
elo
p
in
g
co
u
n
tr
ies,
b
u
t
also
in
d
ev
elo
p
ed
co
u
n
tr
ie
s
wh
er
e
m
o
d
er
n
m
ed
ici
n
e
s
ar
e
p
r
ed
o
m
i
n
a
n
tl
y
u
s
ed
(
R
o
u
t
et
a
l
,
2
0
1
2
)
.
T
h
is
s
tu
d
y
e
x
p
lo
r
es
th
e
p
o
s
s
i
b
ilit
y
o
f
u
ti
lizi
n
g
t
h
e
p
la
n
t
A
.
p
a
n
icu
la
t
a
ac
tiv
e
p
r
in
cip
les
i
n
m
ed
icin
e
to
r
ed
u
ce
th
e
d
r
u
g
r
esis
tan
c
e
p
r
o
b
lem
b
y
E
SB
L
p
at
h
o
g
e
n
s
.
T
h
e
p
lan
t is
r
ep
o
r
ted
to
p
o
s
s
ess
p
r
o
tectiv
e
ac
tiv
it
y
ag
ain
s
t
v
ar
io
u
s
li
v
er
d
is
o
r
d
er
s
.
I
t
is
u
s
ed
to
tr
ea
t
g
a
s
tr
o
in
te
s
tin
a
l
tr
ac
t
a
n
d
u
p
p
er
r
esp
ir
ato
r
y
tr
ac
t
in
f
ec
tio
n
s
,
f
ev
er
,
h
er
p
es,
s
o
r
e
th
r
o
at,
h
e
p
atitis
an
d
a
v
ar
iet
y
o
f
o
t
h
er
ch
r
o
n
ic
an
d
u
p
p
er
r
esp
ir
ato
r
y
tr
ac
t
i
n
f
ec
tio
n
s
(
C
h
o
p
r
a
et
a
l.,
1
9
5
6
)
.
I
t
ex
h
i
b
its
an
tib
ac
ter
ial,
f
ilar
icid
al,
a
n
tid
iar
r
h
o
ea
l,
i
m
p
r
o
v
e
s
ca
r
d
io
v
asc
u
lar
ac
ti
v
itie
s
,
f
er
tili
t
y
an
d
g
iv
e
s
p
r
o
tectio
n
to
liv
er
an
d
g
all
b
lad
d
er
.
T
h
e
h
er
b
an
d
its
is
o
lates
lik
e
an
d
r
o
g
r
ap
h
o
lid
e,
n
eo
g
r
ap
h
o
lid
e,
etc.
ar
e
r
ep
o
r
ted
to
p
o
s
s
ess
an
ti
-
in
f
la
m
m
ato
r
y
,
h
ep
ato
-
p
r
o
tectiv
e,
a
s
tr
i
n
g
e
n
t,
an
o
d
y
n
e,
to
n
ic,
alex
ip
h
o
r
m
ic
an
d
an
ti
p
y
r
eti
c
p
r
o
p
er
ties
an
d
h
elp
s
in
ar
r
esti
n
g
d
y
s
e
n
ter
y
,
c
h
o
ler
a,
d
iab
etes,
in
f
lu
e
n
za
,
b
r
o
n
ch
itis
,
s
w
elli
n
g
s
an
d
itc
h
es,
p
iles
a
n
d
g
o
n
o
r
r
h
o
ea
(
P
r
a
j
ap
ati
et
a
l
.
,
2
0
0
3
)
.
Flav
o
n
o
id
s
p
r
esen
t
i
n
p
la
n
t
s
h
o
w
ed
p
o
ten
t
in
h
ib
itio
n
o
f
co
llag
en
,
ar
ac
h
id
o
n
ic
ac
id
,
th
r
o
m
b
i
n
an
d
p
latelet
ag
g
r
eg
at
io
n
(
W
u
et
a
l.,
2
0
0
8
)
.
T
h
e
p
r
im
ar
y
m
ed
icin
al
co
n
s
ti
tu
en
ts
o
f
A
.
p
a
n
icu
la
ta
ar
e
an
d
r
o
g
r
ap
h
o
lid
e
an
d
r
elate
d
co
m
p
o
u
n
d
s
w
h
ic
h
ar
e
d
iter
p
en
io
d
s
s
h
o
w
i
n
g
a
n
tip
y
r
etic,
an
ti
-
i
n
f
la
m
m
ato
r
y
,
i
m
m
u
n
o
s
ti
m
u
lato
r
y
a
n
d
a
n
ti
ca
n
ce
r
o
u
s
ac
tiv
ities
(
Mish
r
a
et
a
l
.
,
2
0
0
9
; Sax
en
a,
2
0
0
0
; K
u
m
ar
et
a
l
.
,
2
0
0
4
)
.
T
h
e
p
r
esen
t
s
tu
d
y
u
n
d
er
tak
e
n
to
in
v
esti
g
ate
th
e
p
la
n
t
ac
tiv
e
co
m
p
o
u
n
d
o
f
f
r
ac
tio
n
s
w
h
o
s
e
b
in
d
in
g
p
r
o
p
er
ties
w
a
s
s
t
u
d
ied
I
n
s
ili
co
p
r
o
v
id
es
an
in
it
ial
s
tep
to
w
ar
d
s
t
h
e
d
ev
elo
p
m
e
n
t
o
f
a
n
o
v
el
d
r
u
g
m
o
lec
u
le
th
at
ca
n
co
m
p
eti
v
el
y
b
i
n
d
t
o
th
e
ac
ti
v
e
s
ite
o
f
E
SB
L
g
e
n
es
T
E
M
52
,
C
T
X
-
M
13
an
d
SHV
1
.
T
h
e
an
ti
m
icr
o
b
ial
ac
tiv
i
t
y
p
o
te
n
tia
l
o
f
A
.
p
a
n
icu
la
ta
h
as
b
ee
n
d
eter
m
in
ed
a
n
d
th
e
ac
t
iv
e
p
r
i
n
cip
les
r
esp
o
n
s
ib
le
f
o
r
th
e
ac
ti
v
it
y
h
a
v
e
b
ee
n
is
o
lated
an
d
ch
ar
ac
ter
ized
b
y
FT
I
R
an
d
GC
MS
s
p
ec
tr
u
m
a
n
al
y
s
i
s
.
2.
M
AT
E
RIAL
S AN
D
M
E
T
H
O
DS
I
n
o
r
d
er
to
d
et
er
m
i
n
e
t
h
e
b
i
n
d
in
g
en
er
g
y
o
f
ac
ti
v
e
co
m
p
o
u
n
d
s
c
h
ar
ac
ter
ized
b
y
FT
I
R
a
n
d
G
C
M
S
s
p
ec
tr
u
m
a
n
al
y
s
i
s
r
esp
o
n
s
ib
le
f
o
r
th
e
an
tib
ac
ter
ial
ac
ti
v
it
y
ag
ain
s
t
E
SB
L
s
T
E
M
52
,
C
T
X
–
M
13
&
SHV
12
a
m
o
lecu
lar
d
o
ck
i
n
g
ca
lc
u
latio
n
w
as
d
o
n
e
i
n
DOCKIN
G
W
E
B
SERVER
(
www
.
d
o
ck
i
n
g
s
er
v
er
.
co
m
)
.
T
h
e
s
tep
s
ca
r
r
ied
o
u
t
as
t
h
e
p
r
o
tein
s
tr
u
ctu
r
e
T
E
M
52
r
eq
u
ir
ed
f
o
r
d
o
ck
in
g
p
r
o
ce
d
u
r
e
w
er
e
d
o
w
n
lo
ad
ed
f
r
o
m
P
r
o
tein
Data
B
an
k
C
T
X
–
M
13
s
tr
u
ctu
r
e
w
a
s
h
o
m
o
lo
g
y
b
u
i
lt
b
y
u
s
i
n
g
SW
I
SS
p
r
o
tei
n
m
o
d
el
s
er
v
er
,
Evaluation Warning : The document was created with Spire.PDF for Python.
I
SS
N
:
2
2
5
2
-
8814
IJ
AA
S
Vo
l.
3
,
No
.
3
,
Sep
tem
b
er
2
0
1
4
:
15
1
–
15
7
154
SHV1
2
s
tr
u
ct
u
r
e
w
as
o
b
tain
ed
f
r
o
m
P
r
o
tei
n
Mo
d
el
P
o
r
tal
(
P
r
o
tein
Mo
d
el
P
o
r
tal:www
.
p
r
o
tein
m
o
d
elp
o
r
tal.
o
r
g
/q
u
e
y
/
u
n
ip
r
o
t/A
6
T
I
K7
)
.
T
h
e
ac
tiv
e
co
m
p
o
u
n
d
s
s
h
o
wn
i
n
h
ig
h
est
p
ea
k
c
h
ar
ac
ter
ized
b
y
FT
I
R
an
d
GC
An
al
y
s
is
is
1
3
–
Hex
y
lo
x
ac
y
clo
tr
id
ec
1
0
–
E
n
–
On
e,
t
h
e
s
tr
u
ctu
r
e
o
f
th
is
co
m
p
o
u
n
d
w
as
d
r
a
w
n
w
it
h
c
h
e
m
ical
d
r
a
w
i
n
g
to
o
ls
s
u
c
h
as
s
a
v
ed
in
„
m
o
l
‟
f
i
le
f
o
r
m
at
an
d
t
h
e
b
io
lo
g
ical
ac
tiv
i
t
y
o
f
th
e
co
m
p
o
u
n
d
w
as
p
r
ed
icted
an
d
A
b
s
o
r
p
tio
n
Dis
tr
ib
u
tio
n
Me
tab
o
lis
m
E
x
cr
etio
n
an
d
T
o
x
icity
(
A
DM
E
T
)
p
r
o
p
er
ties
w
er
e
an
al
y
ze
d
th
r
o
u
g
h
co
m
p
u
tatio
n
a
l
m
et
h
o
d
s
ADM
E
T
s
er
v
er
(
h
ttp
://p
r
ea
d
m
e
t.b
m
d
r
c.
o
r
g
/
)
.
Dr
u
g
lik
en
e
s
s
o
f
t
h
i
s
co
m
p
o
u
n
d
w
as
test
ed
w
it
h
W
DI
r
u
le
an
d
L
ip
in
s
k
i
‟
s
r
u
le
5
an
d
r
ev
ea
led
th
at
13
-
h
e
x
y
l o
x
y
c
y
cl
o
tr
id
ec
-
10
-
en
-
2
-
o
n
e,
w
o
u
ld
s
er
v
e
as a
n
e
f
f
ec
tiv
e
co
m
p
o
u
n
d
ag
ai
n
s
t E
SB
L
s
.
T
h
e
MM
FF
9
4
(
Halg
r
en
,
1
9
9
8
)
w
a
s
u
s
ed
f
o
r
e
n
er
g
y
m
in
i
m
izatio
n
o
f
lig
a
n
d
m
o
lecu
le.
Gasteig
er
p
ar
tial
ch
ar
g
e
s
w
er
e
ad
d
ed
to
th
e
li
g
a
n
d
ato
m
s
.
No
n
p
o
lar
h
y
d
r
o
g
e
n
ato
m
s
w
er
e
m
er
g
ed
a
n
d
r
o
tatab
le
b
o
n
d
s
w
er
e
d
ef
i
n
ed
.
Do
ck
in
g
ca
lc
u
latio
n
s
w
er
e
ca
r
r
ied
o
u
t
o
n
T
E
M
52
,
C
T
X
-
M
13
an
d
SHV
12
p
r
o
tein
m
o
d
els.
E
s
s
en
tial
h
y
d
r
o
g
en
ato
m
s
,
Ko
ll
m
a
n
u
n
ited
ato
m
t
y
p
e
c
h
ar
g
es
an
d
s
o
lv
atio
n
p
ar
a
m
eter
s
w
er
e
ad
d
ed
w
ith
t
h
e
aid
o
f
Au
to
Do
ck
to
o
ls
i
m
p
le
m
en
ted
in
d
o
ck
in
g
s
er
v
er
.
Af
f
in
it
y
(
g
r
id
)
m
ap
s
o
f
2
0
x
2
0
x
2
0
A
o
g
r
id
p
o
in
ts
a
n
d
0
.
3
7
5
A
o
s
p
ac
in
g
w
er
e
g
e
n
e
r
ated
u
s
in
g
th
e
Au
to
g
r
id
p
r
o
g
r
a
m
.
Au
to
Do
ck
p
ar
a
m
eter
s
et
an
d
d
is
tan
ce
-
d
ep
en
d
en
t
d
ielec
tr
ic
f
u
n
ctio
n
s
w
er
e
u
s
e
in
t
h
e
ca
lcu
latio
n
o
f
th
e
Van
d
er
W
aa
ls
an
d
th
e
elec
tr
o
s
tatic
ter
m
s
r
esp
ec
tiv
el
y
.
E
ac
h
d
o
ck
i
n
g
e
x
p
er
i
m
e
n
t
w
as
d
er
i
v
ed
f
r
o
m
1
0
d
if
f
er
en
t
r
u
n
s
t
h
at
w
er
e
s
et
to
ter
m
in
ate
a
f
ter
a
m
ax
i
m
u
m
o
f
2
5
0
0
0
0
en
er
g
y
ev
alu
a
tio
n
s
a
n
d
t
h
e
b
in
d
i
n
g
e
n
er
g
ie
s
i
n
d
i
f
f
er
en
t
p
o
s
es
o
f
i
n
ter
ac
tio
n
o
f
1
3
–
Hex
y
lo
x
ac
y
clo
tr
id
ec
-
10
–
E
n
–
On
e
to
E
SB
L
s
w
er
e
ca
lcu
la
ted
.
3.
RE
SU
L
T
S AN
D
D
I
SCU
SS
I
O
NS
T
h
e
th
r
ee
d
im
en
s
io
n
a
l
s
tr
u
ctu
r
e
o
f
b
eta
lacta
m
a
s
e
T
E
M
52
w
as
d
eter
m
i
n
ed
u
s
in
g
X
-
r
a
y
cr
y
s
tallo
g
r
ap
h
y
m
et
h
o
d
.
Ho
m
o
lo
g
y
m
o
d
eli
n
g
o
f
C
T
X
-
M
-
13
B
last
-
P
w
a
s
p
er
f
o
r
m
ed
ag
ain
s
t
P
r
o
tein
Data
B
an
k
to
r
etr
iev
e
s
u
itab
le
te
m
p
lates
f
o
r
h
o
m
o
lo
g
y
m
o
d
elin
g
t
h
e
C
T
X
-
M
-
13
s
eq
u
e
n
ce
o
b
tain
ed
f
r
o
m
Gen
b
a
n
k
ac
ce
s
s
io
n
n
u
m
b
er
s
AF2
5
2
6
2
3
.
B
ased
o
n
t
h
e
E
-
s
co
r
e
P
D
B
-
I
YS
A
w
a
s
c
h
o
s
e
n
a
s
te
m
p
late
f
o
r
m
o
d
elin
g
.
Mo
d
els
w
er
e
p
r
ep
ar
ed
u
s
in
g
S
w
is
s
Mo
d
el
Ser
v
er
(
A
r
n
o
ld
et
a
l
.
,
2
0
0
6
)
an
d
v
er
if
ied
b
y
P
r
o
ch
ec
k
.
R
a
m
P
ag
e
w
a
s
u
s
ed
to
p
r
ep
ar
e
R
am
ac
h
a
n
d
r
an
p
lo
ts
(
Fig
.
1
)
.
Ov
er
9
0
%
o
f
th
e
a
m
in
o
ac
id
r
esid
u
es
i
n
t
h
e
p
r
o
tein
s
tr
u
ct
u
r
e
m
o
d
eled
f
r
o
m
C
T
X
-
M
-
13
g
en
e
w
er
e
f
o
u
n
d
to
b
e
p
r
esen
t
i
n
th
e
m
o
s
t
f
a
v
o
u
r
ab
le
r
eg
io
n
s
a
s
r
ev
ea
led
b
y
th
e
ir
r
esp
ec
tiv
e
R
a
m
ac
h
a
n
d
r
an
p
l
o
ts
.
Mo
d
eled
Stru
ct
u
r
e
o
f
S
HV
12
w
as
o
b
tain
ed
f
r
o
m
P
r
o
tein
Mo
d
el
P
o
r
tal
(
P
r
o
tein
Mo
d
el
P
o
r
tal
:
w
ww
.
p
r
o
te
in
m
o
d
elp
o
r
tal.
o
r
g
/q
u
e
y
/
u
n
ip
r
o
t/A
6
T
I
K7
).
T
h
e
lig
a
n
d
m
o
lec
u
le
13
-
h
e
x
y
l
o
x
a
c
y
clo
tr
id
ec
-
10
-
en
-
2
-
o
n
e
in
c
lu
d
ed
i
n
t
h
i
s
s
tu
d
y
w
a
s
o
b
tain
e
d
f
r
o
m
et
h
an
o
l
e
x
tr
ac
t
o
f
A
n
d
r
o
g
r
a
p
h
is
p
a
n
icu
la
ta
w
h
ic
h
s
h
o
w
ed
th
e
h
i
g
h
e
s
t
p
ea
k
v
alu
e
in
t
h
e
Ma
s
s
Sp
ec
tr
o
m
e
tr
y
an
a
l
y
s
is
.
T
h
e
s
tr
u
ctu
r
e
o
f
t
h
i
s
co
m
p
o
u
n
d
w
a
s
d
r
a
w
n
w
i
th
c
h
e
m
ical
d
r
a
w
i
n
g
to
o
ls
s
u
c
h
as
s
a
v
ed
in
„
m
o
l
‟
f
ile
f
o
r
m
at.
T
h
e
b
io
lo
g
ical
ac
tiv
i
t
y
o
f
t
h
e
co
m
p
o
u
n
d
w
as
p
r
ed
icted
an
d
A
b
s
o
r
p
tio
n
Dis
tr
ib
u
tio
n
Me
tab
o
lis
m
E
x
cr
etio
n
an
d
T
o
x
icit
y
(
A
DM
E
T
)
p
r
o
p
er
ties
w
er
e
an
al
y
ze
d
th
r
o
u
g
h
co
m
p
u
tatio
n
al
m
eth
o
d
s
A
DM
E
T
s
er
v
er
(
h
ttp
://p
r
ea
d
m
et.
b
m
d
r
c.
o
r
g
/
)
Dr
u
g
li
k
e
n
es
s
o
f
t
h
is
co
m
p
o
u
n
d
w
a
s
tes
te
d
w
it
h
W
DI
r
u
le
a
n
d
L
ip
i
n
s
k
i
‟
s
r
u
le
5
an
d
r
ev
ea
le
d
th
at
13
-
h
e
x
y
l
o
x
a
c
y
clo
tr
i
d
ec
-
10
-
en
-
2
-
o
n
e
w
o
u
ld
s
er
v
e
as
a
d
r
u
g
–
li
k
e
co
m
p
o
u
n
d
.
T
h
e
p
r
ed
icte
d
p
r
o
p
er
ties
o
f
1
3
-
h
e
x
y
l o
x
a
c
y
clo
t
r
id
ec
-
10
-
en
-
2
-
o
n
e
ar
e
s
h
o
w
n
i
n
T
ab
le
1.
T
ab
le
1
.
P
r
ed
icted
P
r
o
p
er
ties
o
f
1
3
–
Hex
y
lo
x
ac
y
clo
tr
id
ec
-
10
–
E
n
–
o
n
e
C
a
l
c
u
l
a
t
e
d
P
r
o
p
e
r
t
i
e
s
1
3
–
Hex
y
l
o
x
a
c
y
c
l
o
t
r
i
d
e
c
-
1
0
–
E
n
–
o
n
e
M
o
l
e
c
u
l
a
r
F
o
r
mu
l
a
C
18
H
32
O
2
M
o
l
e
c
u
l
a
r
W
e
i
g
h
t
2
8
9
M
o
l
a
r
V
o
l
u
me
3
2
5
.
3
9
L
o
g
P
4
.
2
9
H
y
d
r
o
g
e
n
b
o
n
d
a
c
c
e
p
t
o
r
s
i
t
e
3
H
y
d
r
o
g
e
n
b
o
n
d
d
o
n
o
r
si
t
e
1
P
a
r
t
i
a
l
p
o
si
t
i
v
e
a
r
e
a
3
2
4
.
5
9
P
a
r
t
i
a
l
n
e
g
a
t
i
v
e
a
r
e
a
1
6
0
.
3
5
H
y
d
r
o
p
h
o
b
i
c
su
r
f
a
c
e
4
4
6
.
5
2
1
S
u
r
f
a
c
e
a
r
e
a
o
n
d
o
n
o
r
H
y
d
r
o
g
e
n
a
t
o
m
s
1
0
.
3
2
4
C
h
a
r
g
e
o
n
d
o
n
a
t
a
b
l
e
H
y
d
r
o
g
e
n
s
0
.
3
4
0
7
0
6
P
o
l
a
r
su
r
f
a
c
e
a
r
e
a
3
4
.
1
6
2
H
y
d
r
o
p
h
o
b
i
c
su
r
f
a
c
e
a
r
e
a
2
4
9
W
i
e
n
e
r
I
n
d
e
x
1
0
3
1
L
i
p
i
n
sk
i
‟
s R
u
l
e
o
f
F
i
v
e
S
u
i
t
a
b
l
e
Do
ck
in
g
s
ti
m
u
latio
n
s
w
er
e
p
er
f
o
r
m
ed
u
s
i
n
g
th
e
L
a
m
ar
ck
ia
n
Gen
etic
A
l
g
o
r
ith
m
(
L
G
A
)
a
n
d
th
e
So
lis
an
d
W
ets
lo
ca
l
m
et
h
o
d
.
I
n
iti
al
p
o
s
itio
n
,
o
r
ien
ta
tio
n
a
n
d
t
o
r
s
io
n
s
o
f
th
e
li
g
an
d
(
Sri
v
as
tav
a
et
a
l
.
,
2
0
1
0
)
m
o
lecu
le
s
s
et
r
an
d
o
m
l
y
.
E
ac
h
d
o
ck
in
g
ex
p
er
i
m
en
t
w
as
d
er
iv
ed
f
r
o
m
1
0
d
if
f
er
e
n
t
r
u
n
s
th
at
w
er
e
s
et
to
Evaluation Warning : The document was created with Spire.PDF for Python.
IJ
AA
S
I
SS
N:
2252
-
8814
I
n
s
ilico
I
d
en
tifi
ca
tio
n
o
f P
o
ten
t I
n
h
ib
ito
r
fr
o
m
A
n
d
r
o
g
r
a
p
h
is
P
a
n
icu
la
ta
f
o
r
E
S
B
Ls
(
A
ysh
a
O.
S
)
155
ter
m
i
n
ate
a
f
ter
a
m
a
x
i
m
u
m
o
f
2
5
0
0
0
0
en
er
g
y
ev
a
lu
at
io
n
s
.
T
h
e
p
o
p
u
latio
n
s
ize
w
a
s
s
et
to
1
5
0
.
Du
r
in
g
t
h
e
s
ea
r
ch
,
a
tr
an
s
la
tio
n
al
s
tep
o
f
0
.
2
an
d
q
u
ater
n
io
n
an
d
to
r
s
io
n
s
t
ep
s
o
f
5
w
er
e
ap
p
lied
(
T
a
b
l
e
2)
.
T
ab
le
2
.
B
est R
an
k
P
o
s
e
R
es
u
lts
Pr
o
t
e
i
n
L
i
g
a
n
d
E
st
i
m
a
t
i
o
n
o
f
f
r
e
e
e
n
e
r
g
y
o
f
b
i
n
d
i
n
g
E
st
i
m
a
t
i
o
n
o
f
i
n
h
i
b
i
t
i
o
n
c
o
n
st
a
n
t
Ki
V
a
n
d
e
r
W
a
l
s+
Hy
d
r
o
g
e
n
b
o
n
d
+D
i
sso
l
v
i
n
g
e
n
e
r
g
y
E
l
e
c
t
r
o
st
a
t
i
c
e
n
e
r
g
y
T
o
t
a
l
In
t
e
r
n
a
l
e
n
e
r
g
y
In
t
e
r
a
c
t
i
n
g
S
u
r
f
a
c
e
T
EM
52
t
o
1
3
H
e
x
y
l
o
x
a
c
y
c
l
o
t
r
i
d
e
c
1
0
-
e
n
2
-
o
n
e
-
3
.
2
7
k
c
a
l
/
mo
l
3
.
9
9
u
M
-
4
.
1
7
k
c
a
l
/
mo
l
-
0
.
3
3
k
c
a
l
/
mo
l
-
4
.
5
0
k
c
a
l
/
mo
l
6
0
0
.
3
7
3
C
T
X
–
M
13
t
o
1
3
H
e
x
y
l
c
y
c
l
o
t
r
i
d
e
c
1
0
-
e
n
2
-
o
n
e
-
4
.
9
5
k
c
a
l
/
mo
l
2
3
6
.
4
3
u
M
-
5
.
7
5
k
c
a
l
/
mo
l
-
0
.
4
4
k
c
a
l
/
mo
l
-
6
.
1
9
k
c
a
l
/
mo
l
6
3
8
.
3
2
3
S
H
V
12
t
o
1
3
H
e
x
y
l
c
y
c
l
o
t
r
i
d
e
c
1
0
-
e
n
2
-
o
n
e
-
4
.
6
7
k
c
a
l
/
mo
l
3
7
9
.
6
5
u
M
-
5
.
1
1
k
c
a
l
/
mo
l
-
0
.
9
5
k
c
a
l
/
mo
l
-
6
.
0
6
k
c
a
l
/
mo
l
-
.
T
h
e
m
o
lec
u
lar
b
asis
o
f
i
n
ter
a
ctio
n
an
d
af
f
i
n
it
y
o
f
b
in
d
i
n
g
o
f
T
E
M
52
,
C
T
X
–
M
13
an
d
SHV
12
to
th
e
p
o
ten
t
lig
a
n
d
1
3
-
Hex
y
l
c
y
clo
tr
id
ec
-
10
–
2
-
en
-
o
n
e
f
r
o
m
A
n
d
r
o
g
r
a
p
h
is
p
a
n
icu
l
a
ta
.
T
h
ese
w
er
e
d
o
ck
ed
in
to
th
e
ac
ti
v
e
s
i
te
o
f
o
f
T
E
M
52
,
C
T
X
-
M
13
an
d
SHV
12
.
Fi
g
.
2
,
3
&
4
r
ep
r
esen
ts
i
n
ter
ac
tio
n
o
f
1
3
Hex
y
l
o
x
a
c
y
clo
tr
id
ec
1
0
-
en
-
2
-
O
n
e
&
T
E
M
52
.
Fig
u
r
e
3
.
I
n
ter
ac
tio
n
o
f
1
3
Hex
y
l o
x
a
c
y
clo
tr
id
ec
1
0
–
en
–
2
-
On
e
&
C
T
X
-
M
13
Fig
u
r
e
4
.
I
n
ter
ac
tio
n
o
f
1
3
He
x
y
l
o
x
a
c
y
c
lo
tr
id
ec
1
0
–
en
–
2
-
o
n
e
&
SHV
12
T
h
e
d
o
ck
in
g
r
es
u
lt
s
p
r
o
v
ed
th
at
t
h
e
a
m
in
o
ac
id
r
esid
u
e
s
Se
r
7
0
,
Ser
1
3
0
,
Ser
1
2
6
,
A
r
g
2
7
6
an
d
T
h
r
2
3
1
,
T
h
r
2
3
5
o
f
T
E
M
52
,
C
T
X
-
M
15
an
d
SHV
12
m
a
k
e
i
m
p
o
r
tan
t
co
n
tact
w
i
th
t
h
e
li
g
a
n
d
.
I
n
a
d
o
ck
in
g
s
tu
d
y
co
n
d
u
cted
b
y
S
h
ak
i
l
et
a
l
.
,
(
2
0
1
0
)
,
th
e
a
m
i
n
o
ac
id
r
esid
u
e
s
As
n
1
3
2
,
Glu
1
6
6
,
P
r
o
1
6
7
,
V
al1
7
2
,
L
y
s
2
3
4
an
d
T
h
r
2
3
5
m
ak
e
i
m
p
o
r
tan
t
co
n
ta
ct
w
it
h
ce
f
o
tax
i
m
e
th
er
eb
y
r
es
is
t
t
h
e
t
h
ir
d
g
en
er
atio
n
ce
p
h
al
o
s
p
o
r
in
d
r
u
g
s
.
T
h
e
p
r
esen
t
i
n
v
esti
g
atio
n
al
s
o
g
a
v
e
a
v
er
y
g
o
o
d
id
ea
ab
o
u
t
t
h
e
p
r
ese
n
ce
o
f
a
m
in
o
ac
id
s
in
m
o
s
t
f
a
v
o
u
r
ab
le
r
eg
io
n
s
r
ev
ea
led
b
y
t
h
e
r
esp
e
ctiv
e
R
a
m
ac
h
a
n
d
r
an
p
lo
t
(
a
n
d
th
e
a
m
in
o
ac
id
r
esid
u
e
s
S
er
7
0
,
Ser
1
3
0
Ser
1
2
6
,
A
r
g
2
7
6
,
T
h
r
2
3
1
an
d
T
h
r
2
3
5
o
f
T
E
M
52
,
C
T
X
-
M
15
a
n
d
SHV
12
m
ak
e
i
m
p
o
r
tan
t
co
n
t
ac
t
w
it
h
1
3
Hex
y
l
o
x
a
c
y
c
lo
tr
id
ec
1
0
–
e
n
–
2
-
o
n
e.
Si
n
ce
1
3
He
x
y
l
o
x
a
c
y
cl
o
tr
id
ec
1
0
–
en
–
2
-
o
n
e
is
a
b
le
to
co
n
tact
s
w
i
t
h
th
ese
a
m
i
n
o
ac
id
s
an
d
th
i
s
co
u
ld
b
e
a
p
o
ten
t d
r
u
g
ag
a
in
s
t E
S
B
L
s
tr
ain
s
.
4.
CO
NCLU
SI
O
N
I
n
an
i
n
v
e
s
ti
g
atio
n
b
y
Dais
y
et
a
l
.
,
(
2
0
0
8
)
,
th
e
p
r
o
tein
a
u
t
o
ly
s
i
n
f
r
o
m
E
SB
L
s
tr
ai
n
S
ta
p
h
ylo
co
o
c
u
s
a
u
r
eu
s
w
a
s
d
o
ck
ed
w
it
h
t
h
e
ter
p
en
o
id
f
r
o
m
E
lep
h
a
n
to
p
u
s
s
ca
b
er
an
d
f
o
u
n
d
t
h
at
ter
p
en
o
id
ca
n
i
n
h
ib
it
t
h
e
ac
tiv
it
y
o
f
a
u
to
l
y
s
i
n
b
y
f
o
r
m
i
n
g
a
s
tr
o
n
g
ato
m
ic
i
n
ter
ac
tio
n
w
it
h
t
h
e
ac
ti
v
e
s
ite
r
esid
u
es.
I
n
th
e
p
r
esen
t
s
t
u
d
y
also
E
SB
L
E
.
co
li
a
n
d
K
.
p
n
eu
mo
n
ia
e
w
er
e
tak
e
n
f
o
r
d
o
ck
in
g
s
t
u
d
y
w
h
ic
h
p
o
s
s
es
th
e
E
SB
L
e
n
z
y
m
es.
T
h
e
L
o
g
P
v
alu
e
o
f
1
3
-
Hex
y
l
c
y
clo
tr
id
ec
-
10
-
en
-
2
o
n
e
w
as
f
o
u
n
d
to
b
e
4
.
2
9
w
h
ic
h
r
ese
m
b
les
ter
p
en
o
id
f
r
o
m
E
lep
h
a
n
to
p
u
s
s
ca
b
er
an
d
s
o
b
ec
au
s
e
o
f
t
h
is
p
ar
titi
o
n
co
e
f
f
i
cien
t
t
h
is
li
g
an
d
ca
n
b
r
ea
k
u
p
th
e
ce
ll
w
all
o
f
t
h
e
o
r
g
an
is
m
s
a
n
d
p
en
etr
ate
t
h
e
m
.
I
n
p
r
esen
t
s
ce
n
ar
io
,
th
e
o
n
g
o
i
n
g
f
i
g
h
t
ag
ai
n
s
t
m
u
ltid
r
u
g
r
es
is
tan
t
m
icr
o
o
r
g
a
n
is
m
s
h
as
r
ec
eiv
ed
a
s
et
b
ac
k
to
g
e
n
er
ate
a
p
o
ten
t
d
r
u
g
.
T
h
er
ef
o
r
e,
s
t
u
d
ies
ar
e
b
ei
n
g
ca
r
r
ied
o
u
t
in
v
ar
io
u
s
p
ar
ts
o
f
w
o
r
ld
to
f
in
d
a
n
alter
n
ati
v
e
v
iab
le
d
r
u
g
w
h
ic
h
ca
n
co
m
e
in
to
r
esc
u
e.
T
h
is
lig
a
n
d
m
a
y
b
e
s
u
ch
a
p
o
ten
t
o
n
e.
E
x
p
er
i
m
en
ta
l
in
v
e
s
ti
g
atio
n
s
ar
e
s
til
l
ca
r
r
ied
o
u
t
to
v
alid
ate
t
h
e
f
i
n
d
i
n
g
s
f
r
o
m
i
n
s
ilico
ap
p
r
o
ac
h
es.
Hen
ce
th
e
co
m
p
o
u
n
d
1
3
-
Hex
y
l
c
y
clo
tr
id
ec
-
10
-
en
-
2
-
o
n
e
f
r
o
m
A
n
d
r
o
g
r
a
p
h
is
p
a
n
icu
l
a
ta
in
th
e
p
r
esen
t
s
t
u
d
y
ca
n
ac
t
as
d
r
u
g
f
o
r
E
SB
L
p
ath
o
g
en
s
an
d
co
u
ld
b
e
p
o
ten
t
ial
d
r
u
g
ag
a
in
s
t
m
u
lt
id
r
u
g
r
es
i
s
tan
t a
n
d
E
SB
L
o
r
g
a
n
is
m
s
.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
SS
N
:
2
2
5
2
-
8814
IJ
AA
S
Vo
l.
3
,
No
.
3
,
Sep
tem
b
er
2
0
1
4
:
15
1
–
15
7
156
Fu
r
t
h
er
in
v
esti
g
atio
n
s
ca
n
b
e
ca
r
r
ied
o
u
t to
p
r
ed
ict
th
e
ac
tiv
it
y
o
n
o
th
er
E
SB
L
p
ath
o
g
en
s
.
T
h
is
ac
ti
v
e
m
o
lecu
le
w
h
o
s
e
b
in
d
i
n
g
p
r
o
p
er
t
y
w
a
s
s
t
u
d
ied
in
s
ilico
p
r
o
v
id
es
an
in
itia
l
s
tep
to
w
ar
d
s
th
e
d
ev
elo
p
m
e
n
t
o
f
a
n
o
v
el
d
r
u
g
m
o
lecu
le
th
a
t
ca
n
co
m
p
etiti
v
el
y
b
i
n
d
to
th
e
ac
t
iv
e
s
ite
o
f
t
h
e
E
SB
L
e
n
z
y
m
e
s
th
er
eb
y
in
h
ib
iti
n
g
b
eta
lacta
m
a
s
e
r
esi
s
tan
ce
.
T
h
r
o
u
g
h
o
u
r
w
o
r
k
w
e
h
av
e
tr
ied
to
p
r
o
v
id
e
an
i
n
s
ilico
b
ased
i
n
v
e
s
ti
g
atio
n
o
n
t
h
e
s
a
m
e
b
y
u
s
in
g
m
o
s
t
r
eliab
le
a
n
d
s
o
p
h
is
t
icate
d
Do
ck
i
n
g
al
g
o
r
ith
m
to
p
r
o
v
id
e
an
i
n
s
i
lico
t
esti
m
o
n
y
an
d
b
asis
to
th
e
ex
p
er
i
m
en
tal
in
v
est
ig
a
tio
n
s
.
He
n
ce
th
e
p
r
ese
n
t
i
n
v
esti
g
a
tio
n
g
iv
e
s
a
clea
r
in
s
i
lico
in
d
icatio
n
a
n
d
ev
id
en
ce
th
at
1
3
-
He
x
y
l
c
y
clo
tr
id
ec
-
10
-
en
-
2
-
o
n
e
f
r
o
m
A
n
d
r
o
g
r
a
p
h
is
p
a
n
icu
l
a
ta
co
u
ld
b
e
a
p
o
ten
tial
d
r
u
g
f
o
r
g
en
er
at
io
n
d
r
u
g
d
ev
elo
p
m
en
t
ag
a
in
s
t
m
u
ltid
r
u
g
r
esis
ta
n
t
an
d
E
SB
L
o
r
g
a
n
is
m
s
.
Fu
r
t
h
e
r
in
v
e
s
ti
g
atio
n
s
ca
n
b
e
ca
r
r
ied
o
u
t
to
p
r
ed
ict
th
e
ac
tiv
it
y
o
f
1
3
-
Hex
y
l
c
y
clo
tr
id
e
c
-
10
-
en
-
2
-
o
n
e
w
ith
t
h
e
o
th
er
tar
g
et
E
SB
L
en
z
y
m
e
s
.
ACK
NO
WL
E
D
G
E
M
E
NT
W
e
th
an
k
Mo
h
a
m
ed
Sath
a
k
T
r
u
s
t
&
Hea
d
o
f
th
e
Dep
ar
t
m
en
t
o
f
B
io
in
f
o
r
m
at
ics
f
o
r
p
r
o
v
id
in
g
lab
f
ac
ilit
ies.
RE
F
E
R
E
NC
E
S
[1
]
Bra
d
f
o
rd
P.
A
.
,
“
Ex
ten
d
e
d
sp
e
c
tru
m
β
–
lac
ta
m
a
se
s
in
th
e
2
1
s
t
c
e
n
tu
ry
:
Ch
a
r
a
c
teriz
a
ti
o
n
,
e
p
id
e
m
io
lo
g
y
a
n
d
d
e
tec
ti
o
n
o
f
t
h
is
im
p
o
rtan
t
re
sista
n
c
e
th
re
a
t,
”
Cli
n
M
icr
o
b
i
a
l
Rev
,
2
0
0
1
,
V
o
l
.
14
,
N
o
.
(
4
)
,
p
p
.
9
3
3
-
9
5
1
.
[2
]
Ch
e
n
g
J.,
e
t
a
l
.
,
“
P
h
e
n
o
ty
p
ic
a
n
d
m
o
lec
u
lar
c
h
a
ra
c
teri
z
a
ti
o
n
o
f
t
wo
n
o
v
e
l
CT
X
-
M
e
n
z
y
m
e
s
c
a
rri
e
d
b
y
Kleb
sie
ll
a
p
n
e
u
m
o
n
i
a
,”
J
M
o
l
Bi
o
l
Rep
,
2
0
1
0
,
Vo
l.
37
,
No
.
3
,
p
p
.
1
2
6
1
-
1
2
6
7
.
[3
]
Ch
o
p
ra
R.
N.,
e
t
a
l
.
,
“
G
lo
s
sa
r
y
o
f
In
d
ia
n
M
e
d
icin
a
l
P
la
n
ts,
”
NIS
CO
M
,
CS
IR
,
Ne
w
De
lh
i,
In
d
ia
,
1
9
5
6
,
p
p
.
1
8
.
[4
]
M
irza
S.
H.,
e
t
a
l
.
,
“
CX
-
M
ES
B
L
e
n
z
y
m
e
in
Esc
h
e
ric
h
ia
c
o
li
f
r
o
m
u
ro
lo
g
y
p
a
ti
e
n
ts
in
Ra
w
a
lp
in
d
i,
P
a
k
istan
,
”
J
Pa
k
M
e
d
Asso
c
,
2
0
0
6
,
p
p
.
5
7
6
-
5
7
8
.
[5
]
T
o
d
a
r
K.
,
“
P
a
th
o
g
e
n
ic
E.
C
o
li
,”
On
li
n
e
T
e
x
tb
o
o
k
o
f
Ba
c
ter
io
l
o
g
y
.
Un
iv
e
rsit
y
o
f
W
isc
o
n
sin
–
M
a
d
is
o
n
,
De
p
a
rtm
e
n
t
o
f
Ba
c
terio
lo
g
y
,
2
0
0
8
,
p
p
.
3
-
6
.
[6
]
P
h
il
i
p
p
o
n
A
.
,
e
t
a
l
.
,
“
Ep
i
d
e
m
io
lo
g
y
o
f
th
e
e
x
ten
d
e
d
sp
e
c
tru
m
β
-
lac
tam
a
se
s
,”
In
fec
t
,
1
9
8
9
,
V
o
l.
17
,
p
p
.
3
4
7
-
3
5
4
.
[7
]
Kira
ti
sin
P
.
,
e
t
a
l
.
,
“
M
o
lec
u
lar
C
h
a
ra
c
teriz
a
ti
o
n
a
n
d
E
p
id
e
m
io
lo
g
y
o
f
Ex
ten
d
e
d
s
p
e
c
tru
m
b
e
ta
-
lac
ta
m
a
se
-
p
ro
d
u
c
in
g
Esc
h
e
ric
h
ia
c
o
li
a
n
d
Kle
b
sie
ll
a
p
n
e
u
mo
n
ia
e
iso
late
s
c
a
u
sin
g
h
e
a
lt
h
c
a
re
-
a
ss
o
c
iate
d
in
f
e
c
ti
o
n
i
n
T
h
a
il
a
n
d
,
w
h
e
re
th
e
CT
X
-
M
f
a
m
il
y
is
En
d
e
m
ic,”
An
ti
mic
ro
b
Ag
e
n
ts
Ch
e
mo
th
e
r
,
2
0
0
8
,
V
o
l
.
52
,
p
p
.
2
8
1
8
-
2
8
2
4
.
[8
]
M
o
rris
A.
K
,
e
t
a
l
.
,
“
A
n
ti
b
io
t
ic
re
sista
n
c
e
su
rv
e
il
lan
c
e
:
a
c
ti
o
n
f
o
r
in
tern
a
ti
o
n
a
l
st
u
d
ies
,”
J
An
ti
mic
ro
b
T
h
e
r
,
2
0
0
2
,
V
o
l
.
49
,
p
p
.
7
-
1
0
.
[9
]
P
o
o
le
K.
,
“
Re
sista
n
c
e
to
β
-
lac
tam
a
n
ti
b
i
o
ti
c
s
,”
Ce
ll
M
o
l
L
if
e
S
c
.
,
2
0
0
4
,
p
p
.
2
2
0
0
-
2
2
2
3
.
[1
0
]
Ka
p
il
A.
,
“
T
h
e
c
h
a
ll
e
n
g
e
o
f
a
n
ti
b
io
ti
c
re
sista
n
c
e
:
N
e
e
d
to
c
o
n
tem
p
late
,
”
In
d
ia
n
J
M
e
d
Res
.
,
2
0
0
5
,
Vo
l.
121
,
p
p
.
83
-
91.
[1
1
]
Ka
m
b
o
j
V.
P.
,
“
He
rb
a
l
M
e
d
icin
e
,
”
Cu
r S
c
,
2
0
0
0
,
V
o
l.
78
,
No
.
1
,
p
p
.
35
-
39.
[1
2
]
P
ra
jap
a
ti
N.
D.,
e
t
a
l
.
,
“
A
h
a
n
d
b
o
o
k
o
f
m
e
d
icin
a
l
p
lan
ts,
”
A
c
o
mp
l
e
te
so
u
rc
e
b
o
o
k
,
Ag
r
o
b
i
o
s
,
Jo
d
h
p
u
r,
In
d
ia,
2
0
0
3
,
p
p
.
4
5
-
4
6
.
[1
3
]
M
ish
ra
Da
sh
A.
P
.
,
e
t
a
l
.
,
“
A
n
ti
-
m
a
laria
l
a
c
ti
v
it
ies
o
f
An
d
ro
g
r
a
p
h
is
p
a
n
ic
u
la
t
a
a
n
d
He
d
y
o
t
is
Co
ry
mb
o
sa
e
x
trac
ts
a
n
d
t
h
e
ir
c
o
m
b
in
a
ti
o
n
w
it
h
c
u
rc
u
m
in
,”
M
a
la
ria
l
J
,
2
0
0
9
,
V
o
l
.
8
,
p
p
.
2
6
.
[1
4
]
A
b
ish
e
k
Nir
a
n
jan
,
e
t
a
l.
,
“
Bio
l
lo
g
ica
l
a
c
ti
v
it
ies
o
f
K
a
l
m
e
g
h
(A
n
d
ro
g
ra
p
h
is
p
a
n
icu
lata
Ne
e
s)
a
n
d
it
s
a
c
ti
v
e
p
rin
c
i
p
les
-
A
re
v
i
e
w
,
”
In
d
ia
n
j
o
u
r
n
a
l
o
f
n
a
t
u
ra
l
p
ro
d
u
c
ts
a
n
d
re
so
u
rc
e
s
,
2
0
1
0
,
V
o
l.
1
,
No
.
2
,
p
p
.
1
2
5
-
1
3
5
.
[1
5
]
S
a
x
e
n
a
S.,
e
t
a
l
.
,
“
Hig
h
-
P
e
rf
o
r
m
a
n
c
e
T
h
in
-
L
a
y
e
r
Ch
ro
m
a
to
g
ra
p
h
ic
A
n
a
l
y
sis
o
f
He
p
a
to
p
ro
tec
ti
v
e
Diterp
e
n
o
id
s
f
ro
m
An
d
ro
g
r
a
p
h
is
p
a
n
icu
la
ta
,”
Ph
y
to
c
h
e
m
A
n
a
l
Ph
y
t
o
c
h
e
m
An
a
l
.
,
2
0
0
0
,
p
p
.
34
-
3
6
.
[1
6
]
Ku
m
a
r
R.
A
.
,
e
t
a
l
.
,
A
n
ti
c
a
n
c
e
r
a
n
d
im
m
u
n
o
stim
u
lato
r
y
c
o
m
p
o
u
n
d
s
f
ro
m
An
d
ro
g
ra
p
h
is
p
a
n
icu
la
ta
,”
J
Et
h
n
o
p
h
.
2
0
0
4
[1
7
]
Ha
lg
re
n
T.
A.
,
“
M
e
rc
k
m
o
lec
u
lar
f
o
rc
e
f
ield
.
I.
Ba
sis,
f
o
r
m
,
sc
o
p
e
,
p
a
ra
m
e
tri
z
a
ti
o
n
,
a
n
d
p
e
rf
o
rm
a
n
c
e
o
f
M
M
F
F
9
4
,”
J
Co
mp
Ch
e
m
,
1
9
9
8
,
V
o
l
.
17
,
N
o
.
5
-
6
,
p
p
.
4
9
0
-
5
1
9
.
[1
8
]
S
riv
a
sta
v
a
V
.
,
e
t
a
l
.
,
“
M
o
lec
u
la
r
d
o
c
k
in
g
st
u
d
ies
o
n
q
u
i
n
a
z
o
li
n
e
a
n
ti
f
o
late
d
e
riv
a
ti
v
e
s
a
s
h
u
m
a
n
th
y
m
id
y
lat
e
s
y
n
th
a
se
in
h
i
b
it
o
rs.
”
Bi
o
in
f
o
rm
a
ti
o
n
,
2
0
1
0
,
V
o
l
.
4
,
p
p
.
3
5
1
-
3
6
5
.
[1
9
]
S
h
a
k
il
S
.,
e
t
a
l
.
,
“
In
f
e
c
ted
f
o
o
t
u
lce
rs
in
m
a
le
a
n
d
fe
m
a
le
d
iab
e
ti
c
p
a
ti
e
n
ts:
a
c
li
n
ico
-
b
io
i
n
f
o
rm
a
ti
v
e
stu
d
y
,”
An
n
Cli
n
M
icr
o
b
i
o
l
A
n
ti
mic
ro
b
,
2
0
1
0
,
Vo
l.
9
,
N
o
.
2.
[2
0
]
Na
th
isu
w
a
n
S
.
,
e
t
a
l
.
,
“
ES
BL
s: E
p
id
e
m
io
lo
g
y
,
d
e
tec
ti
o
n
a
n
d
trea
tme
n
t
,”
Ph
a
rm
a
c
o
t
h
e
ra
p
y
,
2
0
0
1
,
V
o
l
.
21
,
p
p
.
9
2
0
–
92
8.
[2
1
]
Ba
li
E.
B.
,
e
t
a
l
.
,
“
P
h
e
n
o
ty
p
ic
a
n
d
m
o
lec
u
lar
Ch
a
ra
c
teriz
a
ti
o
n
o
f
S
HV
,
T
EM
,
CT
X
-
M
a
n
d
Ex
ten
d
e
d
sp
e
c
tru
m
b
e
ta
-
lac
ta
m
a
s
e
-
p
ro
d
u
c
e
d
b
y
Esc
h
e
ric
h
ia
c
o
li
,
Acin
o
b
a
c
ter
Ba
u
ma
n
n
ii
a
n
d
Kleb
sie
ll
a
p
n
e
u
m
o
n
i
a
e
is
o
lat
e
s
in
a
T
u
rk
ish
h
o
sp
i
tal
,”
Af
ric
a
n
j
o
u
rn
a
l
o
f
mic
r
o
b
i
o
lo
g
y
re
se
a
rc
h
,
2
0
1
0
,
Vo
l.
4
,
No
.
8
,
p
p
.
6
5
0
-
6
5
4
.
[2
2
]
Ro
u
t
J.
,
e
t
a
l.
,
”
M
e
d
icin
a
l
p
lan
ts
o
f
No
rth
Ca
c
h
a
r
Hill
s
d
istri
c
t
o
f
A
s
sa
m
u
se
d
b
y
th
e
Di
m
a
s
a
tri
b
e
,
”
In
d
i
a
n
j
o
u
r
n
a
l
o
f
tra
d
it
i
o
n
a
l
k
n
o
wled
g
e
,
2
0
1
2
,
V
ol
.
11
,
No
.
3
,
p
p
.
5
2
0
-
5
2
7
.
[2
3
]
Wu
T.
S.,
e
t
a
l
.
,
“
F
lav
o
n
o
i
d
s
a
n
d
e
n
t
-
lab
d
a
n
e
d
it
e
r
p
e
n
o
id
s
f
ro
m
An
d
ro
g
ra
p
h
is
Pa
n
icu
l
a
ta
a
n
d
th
e
ir
a
n
ti
p
late
let
a
g
g
r
e
g
a
to
r
y
a
n
d
v
a
so
re
lax
in
g
e
ffe
c
ts
,”
J
.
Asi
a
n
N
a
t
Pr
o
d
Res
.,
2
0
0
8
,
V
o
l
.
10
,
p
p
.
17
-
2
4
.
Evaluation Warning : The document was created with Spire.PDF for Python.
IJ
AA
S
I
SS
N:
2252
-
8814
I
n
s
ilico
I
d
en
tifi
ca
tio
n
o
f P
o
ten
t I
n
h
ib
ito
r
fr
o
m
A
n
d
r
o
g
r
a
p
h
is
P
a
n
icu
la
ta
f
o
r
E
S
B
Ls
(
A
ysh
a
O.
S
)
157
[2
4
]
Da
is
y
P
.
,
e
t
a
l
.
,
“
Ra
y
a
n
A
No
v
e
l
T
e
rp
e
n
o
id
f
ro
m
El
e
p
h
a
n
t
o
p
u
s
S
c
a
b
e
r
–
A
n
t
ib
a
c
teria
l
A
c
ti
v
it
y
o
n
S
ta
p
h
y
l
o
c
o
c
c
u
s
a
u
re
u
s
:
A
S
u
b
s
tan
ti
a
te C
o
m
p
u
tatio
n
a
l
A
p
p
r
o
a
c
h
,
”
I
n
t.
J
.
Bi
o
me
d
S
c
.,
2
0
0
8
,
Vo
l.
4
,
N
o
.
3
,
p
p
.
1
9
6
-
2
0
1
2
.
[2
5
]
A
rn
o
ld
K
.
,
e
t
a
l.
,
“
T
h
e
S
W
IS
S
-
M
OD
EL
W
o
rk
sp
a
c
e
:
A
w
e
b
-
b
a
s
e
d
e
n
v
iro
n
m
e
n
t
f
o
r
p
ro
tein
str
u
c
tu
re
h
o
m
o
lo
g
y
m
o
d
e
li
n
g
,
”
Bi
o
in
fo
rm
a
t
ics
,
2
0
0
6
,
Vo
l.
22
,
p
p
.
1
9
5
-
2
0
1
.
Evaluation Warning : The document was created with Spire.PDF for Python.