►
Description
Open project meeting for Open Source Antibiotics Series 1, the Mur Ligases.
Full Project: https://github.com/opensourceantibiotics/murligase
Relevant GitHub Issue: https://github.com/opensourceantibiotics/murligase/issues/66
On the call: Professor Matthew Todd, Dr Edwin Tse, Yuhang Wang, Kato Leonard, Zige Bu, Shah Choudhury (UCL), Professor Chris Dowson, Laura Diaz Saez (University of Warwick), Lizbe Koekemoer, Dr Lori Ferrins, Dr Joe Eyermann (Northeastern University), Dr Jan Jensen (University of Copenhagen), Dr Chris Swain (Cambridge MedChem Consulting), Dr Jan Abendroth, Dr Bart Staker (SSGCID).
A
Welcome
everybody:
this
is
the
open
source
video
live
games
meeting
on
tuesday,
the
8th
of
february.
We,
yes,
we
have
some
new
people
joining
us.
Do
you
want
to
do
some
intros
just
whipping
around
the
screen?
Is
that
all
right,
that's,
okay?
I
can
get
going.
I
I
met
todd.
I'm
professor
of
drug
discovery
at
university
college,
london.
B
I
A
L
N
A
Okay,
thanks
everybody,
that's
great!
So
shall
I
I'll
just
pop
up
the
agenda
so
that
we
all
know
what
we're
looking
at
and
there's
lots
of
things
obviously
to
talk
about.
I
don't
know
if
anyone
wants
to
lead
off,
because
you've
got
presentation,
that's
relevant
to
what's
here
already.
I
don't
want
to
dictate
the
agenda
necessarily.
Does
anyone
want
to
go
first
here
and
present
new
data?
That's
that's
needed
here.
A
H
I
have
those
dose
response
curves.
I
actually
tried
to
email
them
to
dana
this
morning
and
obviously
found
out
she'd
moved
on
by
her
email
response.
So
I
can
show
those
response
cards
now.
If
you
would
like
to
see
them
yeah,
they
need
to
be
put
up
online,
but
at
the
moment
I'm
trying
to
figure
out
the
best
way
to
actually
show
them,
but
hopefully
I
can
find
it
for
you.
H
Yeah,
so
these
were
the
compounds
from
dana,
which
I
tested
and
showed
the
dual
inhibition
against
marie
and
madi,
and
so
I
have
now
run
the
dos
response,
curves
against
murder,
step
a
galactica
and
unfortunately,
seven
eight
eight
has
started
precipitating
at
37
degrees
c.
So
we
can't
get
a
dose
of
sponsor
code
for
that,
but
the
other
four
which
all
show
dual
inhibition.
We
now
have
these
data
response,
curves
for
and
so
obviously,
as
you
can
see,
759
is
looking
the
most
promising
from
that
and
probably
would
be.
H
A
H
C
A
O
A
H
And
no,
we
didn't
go
all
the
way
up
to
100,
so
we
were
more
interested
in
the
actual
slope,
and
so
we
just
did
the
one
millimolar
which
we
started
with
and
then
went
to
get
the
lower
end.
I
can
increase
it.
Firstly,
we
then
start
have
to
worrying
about
dmso
concentrations
affecting
the
protein
within
the
assays,
because
yeah.
A
For
ed
and
cato,
it
would
be
interesting
to
see
which
compounds
structurally
similar
to
759
gave
nothing
so
just
to
add
to
the
idea
that
we're
getting
a
specific
interaction.
So
if
you've
got
the
the
three
position,
nitrogen
on
the
pyridine
versus
the
the
two,
you
know
similar
compounds
which
were
ineffective.
We
can
learn
a
lot
from
that,
but
that's
nice.
A
O
O
O
This
wasn't
done
in
in
diamond
and
then
I
observed
some
of
the
compost
melted,
but
not
all
of
them,
so
the
ones
that
were
close,
the
closest
to
where
I
added
the
drop
with
the
compound
those
were
melted,
but
the
rest
were
not,
and
then,
in
the
case
of
I
also
incubated
with
adp
and
those
melted.
After,
like
15
minutes
of
incubation,
they
were
gone.
O
I
included
as
well
the
astrocynical
compound
that
I
got
from
juha
and
yeah.
I
mean
in
case
of
the
so
I
got
a
lot
of
data
sets
for
these
compounds.
They
are
all
between
2.3
and
3
armstrong's
resolution
and
I
couldn't
see
any
compound
bound
to
any
of
the
structures,
but
I
saw
a
change
a
change
in
the
conformation,
so
I
can't
see
yeah.
So
this
is
the
structure
basically,
and
the
gray
structure
is
the
one,
the
apo
structure
that
we
were
always
getting.
O
O
So
I
think
it's
worth
following
up
on
the
compounds
and
trying
to
see
if
there's
any
competition
on
them,
18
with
the
atp,
for
example,
yeah.
So
that's
that's
worth
doing.
I
also
set
up
crystals
for
crystallization
plates
crystal
plates
for
co-crystallization
to
try
to
get
these
crystals
in
a
different
way
and
yeah
so,
but
I
couldn't
confirm
the
binding
with
this
experiment
and
then,
in
the
case
of
yeah,
sorry,.
A
Just
a
quick
question
is
the
the
the
picture
you're
showing
on
the
right
of
the
the
change
in
the
confirmation.
Is
that
is
it
basically
the
same
confirmation
in
each
experiment?
You
know
regardless
right,
yeah,
so,
but
and
if
that
that's,
if
that
confirmation
is
changing,
is
there
a
reason
why
that
would
happen?
If
there
was
not
a
compound
bound,
I
mean.
O
O
Yeah
right
and
then
in
the
case
of
e-coli,
nearly
here
so
the
crystals
were
super
nice
since
the
beginning.
This
is
the
condition
in
case
anyone
is
interested,
but
the
reproducibility
was
really
low.
So
I
was
getting
a
two
percent
of
the
drops
with
crystals,
which
is
really
bad
for
x,
cam,
I'm
now
in
15.
O
I
need
to
check
my
last
crystal
plates.
Hopefully
that
will
be
more
and
I'm
getting
there.
So
at
least
we
can
have
a
decent
replaceability,
so
I
can
do
a
first
test
on
x-cam
yeah,
so
the
experiment
for
soaking
was
the
same.
I
sold
compounds
at
the
same
concentration
as
for
the
newer
e
and
these.
In
this
case
I
tested
apoc
crystals
as
well
as
incubation
at
different
time
points
with
dmso,
and
then
I
included
the
astrazeneca
compound
as
well
as
the
dual
inhibitors
and
adp.
O
This
talking
time
is
a
little
different,
so
I
collected
different
crystals
at
different
time
points
up
to
one
hour,
so
I
got
data
sets
for
different
time
points
for
all
of
them.
Now.
What
I
observed
during
the
soaking
is
that
the
crystals
were
looking
where
they
were
cracking
all
the
time,
except
for
the
apo
or
the
mso
controls,
so
the
compound
seems
to
be
doing
something
to
the
crystals.
O
O
This
is
the
ligand
seven,
five,
nine
and
you
will
look
at
the
structure.
Let
me
so
that's
the
compound,
so
I
can
see
this
part
that
part
with
the
bromide-
and
I
can
see
the
50
occupancy,
as
you
can
see
in
these
figure-
there's
a
little
nice
pocket
in
there
and
there's
another
pocket
on
the
back
as
well.
O
So
I
think
we
should
try
to
test
this
system
in
with
a
partial
exchange
library
and
see
if
this
is
reproducible
with
different
compound
series,
because
if
this
is
happening
all
the
time,
we're
gonna
get
a
lot
of
hits
in
this
area.
Then
we
will
have
to
look
into
different
packing
into
a
different
crystallization
system.
O
O
O
Yeah,
so
that's
basically,
it
is
not
a
confirmation
for
often
any
of
the
binding.
I
think
we
should
follow
up
the
essays
with
competition
essays
on
to
confirm
that
you
know
if
there
is
anybody
into
atp
sites,
because
if
there
is
money
on
the
atp
side,
then
it
makes
sense,
decor
crystallization
experiments.
Maybe
they
do
something.
I
have
started
the
crystallization
experiments
as
well,
so
hopefully
we'll
get
something.
O
Yes,
so
that
one
no
ligand
sorry,
this
was
the
seven
four
nine
yeah
yeah,
the
other
one.
I
couldn't
see
it,
but
I
I
saw
the
blobs
of
ethylene
glycol.
That
is
the
cryoprotectant
and
you
know
dmso
as
well.
I
could
see
them
floating
around
between
these
two
pockets
right
yeah
I
can,
and
for
this
compound
I
cannot
really
see
this
area.
This
is
nowhere
to
be
found.
A
I
The
one
thing
I'm
going
to
draw
your
attention
to
because
it
becomes
an
issue
later
on,
is
the
fact
that
adpcp,
which
is
an
atp
analog
with
a
methylene
interposed
between
the
beta
and
the
gamma
phosphorus
atoms,
is
a
particularly
good
inhibitor
of
murray.
That
is
not
really
that
effective
against
modi,
so
spectrophotometrically.
We
have
an
essay
that
works
on
the
various
scan
plate
reader
and
also,
incidentally,
by
in
the
carry
uv,
visible
spectrophotometers.
We
often
use
to
establish
whether
an
accident
is
going
to
work
in
principle.
I
So
fluorometrically
and
I
have
shown
the
schemes
for
both
the
e
on
the
left
and
my
d
on
the
right.
The
assay
gives
a
clear
fluorescent
signal
in
continuous
mode
again,
with
dependence
upon
all
the
substrates,
in
both
from
both
murky
and
murder,
and
also
as
far
as
murray
is
concerned.
Adp
cp
is
a
very
handy
tall
compound,
which
gives
a
very
nice
inhibitory
response
with
an
ic50
under
the
conditions
we're
using
of
around
about
2.25
micromolar.
I
M
I
I
And
but
if
you
compare
not
just
the
full
reaction
against
the
interaction
without
the
substrate,
but
the
full
reaction
against
the
full
reaction
with
the
inhibitor,
you
have
about
0.471
now.
The
problem
with
this
is
that
the
assay
signal
isn't
that
stable.
You
can
see
it's
beginning
to
decline
quite
rapidly
at
this
point,
so
we're
losing
fluorescence
over
time.
I
This
discrimination
decays
as
the
merlion
gates
concentration
increases,
and
you
would
expect
that,
because
even
in
the
presence
of
an
inhibitor
you're
still
accumulating
product
and
the
longer
you
leave
it
at
the
higher
at
a
higher
concentration.
The
less
discrimination
between
with
and
without
inhibitor
ensues.
I
If
you
leave
the
interaction
for
30
minutes,
essentially
you
lose
the
window
entirely.
So
what
we
have
was
a
fairly
user
unfriendly
assay
we
we
could
define
a
zeb
prime.
We
could
see
it,
but
the
parameters
within
which
we
had
to
work
were
quite
tight
and
if
you
talk
to
people
like
the
european
lead
factory,
they
want
stability
of
signal
for
at
least
half
an
hour.
I
I
So
we
investigated
all
of
these,
so
edta
has
a
stop
again
is
not
that
effective
in
this
particular
assay.
So
this
is
a
murray
assay.
The
black
line
is
the
assay
that
we
attempted
to
stop
with
edta.
There
is
a
water
control.
The
drop
in
absorbance
when
we
with
we
have
the
edta
is
simply
because
of
the
volume
dilution
when
we
add
the
inhibitor,
but
clearly
there's
not
there's
no
real
purchase
on
inhibition
over
that.
I
I
I
What
this
meant
was
that
we
would,
because
we
were
using
pmp
to
accurately
reflect
my
reactivity,
because
it
was
stopping
the
reaction.
After
that
point,
we
needed
to
add
a
fair
amount
of
foreign
disease
to
the
assay,
but
in
actual
fact,
when
you
treat
an
assay
with
foreign
with
the
anticipation,
it
would
stop
it,
and
this
is
murky.
Adpcp
proved
to
be
considerably
more
effective
than
foreign
itself.
I
I
You
get
the
same
response
with
murphy
in
this
particular
panel.
This
is
a
murray
assay,
where
I
was
attempting
to
stop
the
hrp
with
sodium,
which
clearly
didn't
work,
but
this
material
a
double
three,
eight,
five,
five
again
it
completely
quenches
the
signal,
and
so
this
appeared
to
be
an
effective
method
for
actually
stopping
the
reaction.
I
Although
at
this
present
point
in
time,
we
do
have
some
issues
with
the
plate,
reader
and
some
of
the
components,
so
this
basically
shows
a
stopped.
I
say
as
data
set
where
we've
looked
at
the
fluorescence
after
zero
and
60
minutes
after
stopping
the
reaction
with
a
double
three
eight,
five,
five
at
zero
and
one
hour,
three
separate
fluorescence
wavelengths
sets
in
this
particular
data
set.
The
assay
hasn't
worked
that
well.
I
D
G
I'll
send
along,
I
mean,
I
guess
the
question
I
would
have
is
you
know,
astrazeneca
random,
your
c
high
throughput
screen
all
the
assay
conditions
were
published,
so
I'm
a
little
curious
about.
You
know
how
that
or
why
that
was
at
least
you
know,
thought
about
in
terms
of
those
essays
that
have
already
been
kind
of
published.
I
There's
a
certain
amount
of
pragmatism
that
goes
around,
so
we've
got
experience
using
amplex
red
in
other
contexts,
for
example
with
pvp
transplantation.
Lessons,
and
in
actual
fact
I
mean,
as
as
I
often
find,
there's
nothing
new
under
the
sun
and
the
idea
of
using
amplex
red
hrp,
xanthine,
oxidase
and
pnp
in
combination
was
actually
published
for
a
hts
actually
from
a
by
gsk
so
given
to
that
appear
to
work
and
give
decent
data.
I
D
I
I
There
are
ways
in
which
you
can
double
that
by
coupling
the
final
product
to
uricase,
which
doubles
the
amount
of
amplex
rate
products,
and
actually,
if
you
titrate
the
phosphate
products
you
get
an
extinction
coefficient
going
on
for
a
hundred
thousand.
So
in
principle
it
could
actually
be
quite
quite
useful.
D
D
So
miniaturization
is
absolutely
essential
given
by
the
money,
so
that
was
that
was
super
important.
Why
we
did
that
saying
that
as
adrian
identified
right
beginning,
we
have
super
robust,
continuous
assays.
So
that's
probably
a
good
point
to
introduce
anita's
talk,
who's
going
to
talk
about
actually
assaying.
Some
compounds.
C
E
E
That's
why
we
just
for
short
calling
it
compound
w
and
adpcp
is
the
compound
that
agent
has
been
referring
to
also
known
as
ampcp
five
adrenaline
methylene
diphosphonate,
which
is
a
good
mo
inhibitor,
and
we
believe
that
compound
w
was
a
good
pseudomonas,
eriginosa,
merci
inhibitor,
so
just
to
confirm
that
our
assays
were
working
and
it
miniaturized
to
10
microliters
as
a
fluorescence
assay
in
a
plate
reader.
I
conducted
these
experiments,
which
just
were
a
snapshot
against
mercy,
cinemas
mercy.
E
We
just
dilute
the
compound
to
10
or
tested
at
a
10
micromolar,
and
you
can
see
that
compared
to
a
dmso
control
compound
w
is
very
inhibitory
so
which
confirmed
previous
reports.
So
it
was
good
to
to
see
that
we
could
reproduce
that
information,
however
adpcp,
which
is
a
good
e
inhibitor,
is
not
very
inhibitory
against
pseudomonas.
Merci,
we
just
also
then
wanted
to
have
a
look
and
have
a
look.
Whether
compound
w
is
actually
effective
against
strep
pneumonia
mercy
and
it's
only
very
slightly
effective
against
the
stroke
pneumonia
mercy.
E
E
E
Then,
because
we
saw
over
here
that,
if
I
just
take
you
back
to
that
slide-
that
it
had
compound
w
demonstrated
31
inhibition
against
mercy,
we
were
wondering
whether,
if
we,
if
there
was
any
synergy,
if
we
added
both
compound
w
and
adpcp,
and
would
it
reduce
the
ic50
even
further
of
in
the
presence
of
no
e,
and
these
are
the
results.
So
the
ic50,
as
we
saw
before
of
compound
with
moe,
is
11.1
micromolar.
E
When
we
reversed
the
order-
and
we
had
adpcp
present
in
the
master
mix
at
its
ic50
concentration,
we
got
what
looked
like
a
very
random
set
of
spots
and
which
we
tested
and
retested,
and
we
still
kept
on
getting
this.
But
if
you
have
a
look
at
the
actual
readings,
they
vary
just
only
slightly
between
about
and
sixteen
hundred
fluorescents
intensity
units
per
minute,
which
is
actually
very
low
level.
E
So
we
were
then
wondering
because
we've
got
such
different
results
when
we
added
it
in
the
other
way
whereby
compound
w
was
in
the
master
mix,
and
then
adpcp
was
added
at
the
different
concentrations.
We
wondered
whether
there
was
actually
an
order
of
there
was
something
related
to
the
order
of
addition
of
these
compounds
to
the
mastermix.
E
We
had
adpcp
already
in
the
master
mix
and
then
added
compound
w
immediately
after
or
five
minutes
later
or
15
minutes
later,
to
give
the
enzyme
more
time
to
to
bind
to
the
compounds,
and
that
is
a
result
that
we
got,
which
confirms
the
previous
findings.
So
when
compound
w
is
added
first,
you
can
see
that
there
is
definitely
a
benefit
of
adding
adp
cp
to
the
mix.
D
D
O
Same
yeah,
I
did
some
analysis,
but
so
it's
in
an
area
that
is
a
loop
and
we
will
need
the
same
structures
for
the
three
of
them.
You
know
adb,
bound
or
analogues
boundary
structures
for
mu
d,
c
and
e
for
the
same
organisms,
and
we
can
do
proper
co,
proper
comparisons,
but
they
are
not
examples
for
the
three
of
them
on
the
same
organism.
O
O
D
P
O
A
Matt
over
to
you
well
we're
running
up
against
the
hours
is.
The
only
problem
is
the
fascinating
data.
Thank
you
just
wanted
to
make
sure
we
have
the
chance,
for
others
to
bring
up
things
that
they
would
like
to
draw
people's
attention
to.
Whilst
we're
in
the
meeting
here,
laura
you've
posted
the
the
spr
results
already
online.
Did
you
want
to
speak
to
those
very
briefly
in
the
last
few
minutes,
because
obviously
they're
quite
important?
This
is
for
the
atomized
components.
O
O
This
one
looks
to
be
the
best
one,
but
the
signal
is
really
weak
and
there
is
some
non-specific
binding
as
well.
So
I
I
think
it's
just
a
weak
binder.
It's
like
I
said
I
overestimated
kd.
Some
compounds
are
showing
as
well
two
binding
sites.
The
second
binding
site
could
be
known
as
a
non-specific
binding
site
or
could
be
relevant.
O
That
would
need
to
be
followed
up
with
more
experiments
and
addition,
competition
essence
in
the
presence
of
a
and
pcp,
and
there
are
some
compounds
that
showed
no
binding
when
the
aed
pcp
was
found,
and
these
are
the
results
summarized
one
of
them.
I
think
the
one
that
is
looking
more
interesting
is
this
one.
At
the
component,
two
one
two:
it
was
high
x,
cam
heat.
O
O
O
So
this
library
will
be
screened
and
I
say
fantastic,
I'm
going
to
screen
all
of
them
and
then
I
will
compare
everything
you
know
what's
happening
and
what
makes
sense
what
doesn't
mix,
and
so
I
can
learn
as
well
how
these
proteins
behave
on
the
sbr
yeah.
It's
just.
You
know
that
was
the
ampcp
binding
with
negative,
binding
yeah.
G
G
G
I
I
understand
exactly
so
the
question
really
the
question
becomes
then
about
you
know
what
conditions
you're
going
to
be
using
in
in
screening,
and
you
know
how
that
impacts,
whether
you
know
your
hit
finding
and
your
output.
That's
all
I'm
just
saying.
There's
this
difference,
it's
a
thousand-fold
difference!
Those
were
subnet.
I
think
I
compound
sub,
almost
seven
nanomolar
in
an
estrogenic
assay,
or
at
least
you
know
three
nanomolar
or
something
like
that
and
you're
reporting
out
like
one
micromolar.
G
I
I
totally
agree
adrian,
I'm
just
I
think
it's
it's
more
of
a
question
about.
Ultimately,
if
you're
running,
assays
and
you're
trying
to
identify
new
hits
new
series,
new
compounds-
and
you
know
how
sensitive
and
how
you
know
at
what
concentration
you're
running
you
know,
substrate,
for
example-
and
you
know,
are
you
gonna
be
competitive
and
are
you?
Are
you
asking
it
too
too
much
to
of
the
compounds
to
do
too
much
in
terms
of
competition.
A
We're
out
of
time,
I'm
afraid
I
just
wanted
to
give
jan
jan
yanson
the
chance
to
talk
about
the
compounds
he
put
up
online,
just
just
the
other
day,
because
they
just
very
briefly
because
they
do
look
pretty
interesting,
they're
all
based
on
the
same
motif.
As
far
as
I
can
tell
that
central
ring
system,
yeah.
J
So
it's
just
to
summarize,
so
this
is
a
basic
genetic
algorithm.
That's
trying
to
find
binders
with
docking,
tumor
c,
where
we
it's.
We
focus
on
primary
amines,
with
fewer
rotate
fewer
than
five
rotational
bonds
to
to
sort
of
keep
keep
it
in
the
cell,
and
so
I've
gone
we've
generated
about
150
molecules
and
I
sort
of
went
through
them
to
try
to
do
a
quality
check
and
also
look
at
synthesizability.
So
this
is
this
is
the
bound
astrazeneca
compound.
J
I
think
this
is
the
w
compound,
so
just
to
give
you
an
idea
of
the
interactions
but
try
to
sort
of
match
these
interactions
and
and
looking
for
those
in
the
dark
process,
so
not
really
matching
them,
but
but
looking
for
them-
and
so
here
is
always
always
the
reference
compound.
So
we
it's.
Actually
the
code
found
one
family
of
compounds
with
this
ring
here
and
this
sort
of
moiety
here
so
being
that
we
force
it
to
have
an
primary
amine.
J
I
think
there's
always
going
to
be
some
some
salt
bridges
with
the
with
the
acetate
here.
So
that's
in
in
all
the
compounds.
So
I
was
focusing
more
here
on
whether
you
know
we
have
some
some
similar
interactions
here
and,
and
there
is
to
the
the
histidine
and
the
asparagine,
which
is
the
same-
the
same
one
here,
and
this
one
of
course,
so
I
ran
it
through
a
retrosynthesis
program.
I'm
not
I'm
not
a
synthetic
chemist,
but
at
least
this
program
claims
that
this
can
be
made
in
one
step
from
from
purchasable
compounds.
J
Whether
that's
accurate
or
not,
I
don't
know
here's
here's
another
one
again
with
the
similar
moiety
here
there's
and
there's
a
lot
of
examples
this
here.
This
is
just
a
slightly
different
synthesis,
but
basically
the
the
thing
is
the
same
binding
here
with
hydrogen
bonds.
In
here
with
a
salt
bridge
and
a
hydrogen
bond,
then
I
looked
for
other
sort
of
binding
motifs.
J
So
here
you
have.
We
have
this
group
here
now
you
have
four
or
five
four
hydrogen
bonds,
depending
on
how
you
count
same
binding
mode
here
with
the
with
the
primary
amine.
This
can
also
be
made
from
purchasable
compounds
in
one
step
and
here's
another
slightly
different
sort
of
binding
same
spot,
all
the
time
for
the
hydrogen
bonds.
These
have
more
hydrogen
bonds.
Maybe
that's
more
promising!
I
don't
know
this
is
a
more
complicated
synthesis,
at
least
according
to
the
retrosynthesis
program,
and
also
there's
some
major
selectivity
issues
here.
J
So
but
I'll
these
are
slightly
updated,
slides,
so
I'll
put
them
up
and
you
can
look
at
them
at
your
leisure.
Here's
another
binding
mode,
slightly
more
complicated,
only
two
hydrogen
bonds
here,
but
now
it
has.
This
up
sorry,
there's
actually
three
hydrogen
bonds
here
now
you're
involved
with
tyrosine
and
there's
also
this
pipe
interaction
which
is
seen
in
the
astrazeneca
compound,
but
again,
a
more
complicated
synthesis.
J
J
Then
you
have
this
one
here
again,
this
looks
slightly
different,
also
a
different
synthetic
route.
So
maybe
one
thing
to
consider
is
you
know
whether
one
can
buy
a
lot
of
derivatives
of
this
just
using
the
same
reaction
to
to
explore
different
compounds
rapidly,
so
these
are
basically
the
the
best
bets,
so
eight
or
seven
compounds
filtered
down
from
15.
These
are
sort
of
our
best
shot
added.
J
We
also
went
through
250
000
compounds
that
you
can
buy
from
enemy
and
they're
in
their
hit
location
and
actually
only
one
of
them
sort
of
looks
promising.
Maybe
that's
this
one
here,
so
it
has.
It
binds
roughly
in
the
same
part
of
the
pocket
as
this
with
hydrogen
bonds
involving
the
same
residues
and
then
it
has
not
a
primary
amine.
We
couldn't
we
couldn't
screen
for
that
in
the
the
library,
but
it
does
have
a
salt
bridge
here.
J
A
A
A
The
the
issue
he
has
the
you
know
the
recent
structures
from
sgcid
and
then
we're
grouped
together
on
on
you,
hangs
in
setting
work,
which
we
haven't
had
time
to
talk
about
yeah,
but
he's
posted
an
update,
the
atom,
wise
issue,
we're
still
looking
at
how
these
compounds
bind,
because
we
haven't
been
able
to
get
anything
back
from
atomwise
about
whether
or
not
they're
surprised
by
the
crystallography
results.
And
this
section
is
the
one
we've
just
been
talking
about.
A
A
We
all
just
saw
and
they're
asking
whether
we
could
support
it
financially
and
they
would
be
able
to
run
the
screen
of
the
european
lead
factory
library,
but
it's
pretty
expensive.
So
there's
no
immediate
way
that
we
can
pay
that
we
were
running
by
some
some
companies,
the
idea
that
we
could
perhaps
ask
them
to
run
it
for
us.
A
So
partners
of
the
european
lead
factory-
and
I
guess
those
conversations
kind
of
ongoing,
but
it
did
make
us
wonder
about
the
value
of
another
big
screen
and
how
much
we
might
get
in
for
the
project
in
terms
of
the
amount
of
money
that
would
take
to
run
that
screen
joe.
You
brought
up
the
idea
of
running
a
focused
kinase
library.
A
D
A
A
Yeah
yeah,
I'm
with
you,
we
we
do
need
to
worry
about
that,
because
I
think
that
the
compound
w
is
not
the
compound.
I
think
it
is
it's
the
compound
that
you
hang
made,
which
is
like
a
z5595,
but
not
so
has
been
busy
making
sure
all
his
compounds
have
osa
codes,
so
the
simple
code,
which
is
then
constant,
I
think
we
need
to
start
starting
to
start
using
that
as
a
way
of
referring
to
compounds
unambiguously.
But
yes,
structures
on
slides
will
be
awesome.
We.
D
A
G
D
G
But
you
know
the
only
only
comment
I
would
make
is
you
know
you
actually
may
be
doing
the
right
essay
and
they
z
may
have
been
doing
the
wrong
one.
I
mean,
if
you
think,
about
the
potency
that
excuse
me,
anita
found
and
the
fact
that
these
compounds
well
I
mean
in
the
end
they
didn't
have
wild
type
nycs,
but
they
did
have
nyc's
when
they
were
added
with,
I
think,
probably
nixon
or
callisto,
and
I
can't
remember
which,
in
terms
of
permeabilizing
the
e
coli,
so
anyway
yeah
this.
This
is
always
a
challenge.