►
Description
Open project meeting for Open Source Antibiotics Series 1, the Mur Ligases.
Full Project: https://github.com/opensourceantibiot...
Relevant GitHub Issue: https://github.com/opensourceantibiotics/murligase/issues/97
On the call: Dr Edwin Tse, Yuhang Wang, Yiwei Wang (UCL), Prof Chris Dowson (chair), Dr Adrian Lloyd and Dr Laura Diaz Saez (University of Warwick), Dr Joe Eyermann, Dr Lori Ferrins (Northeastern University), Bart Staker (SSGCID), Jan Abendroth (UCB Pharma).
A
A
It's
9th
of
May
welcome
to
the
latest
open
source,
antibiotics,
mer,
ligase,
meeting
and
I
will
do
the
usual
thing
of
sharing
a
the
nicely
put
the
issue
for
today's
meeting.
Then
you
can
smile
during
patriotic
of
you
hang
to
put
this
together,
referencing
the
correlation,
and
let
me
just
share
that
it's
got
lots
of
familiar
things
there
and
and
but
that
you
know
again,
there
are
some
important
things
that
we
can
focus
in
on
and
for
some
reason,
I
can
never
find
the
thing
I'm
supposed
to
be
doing.
A
Wait
one
second,
sorry
there.
It
is
all
right
here
we
go
okay,
so
issue
number
97
is
the
one
for
today
and
thanks
everybody
for
posting
lots
of
things
at
the
bottom
there,
which
I'm
sure
we'll
get
to
so
for
references.
Everything
that's
currently
on
the
table
is
here,
but
up
top.
There
are
the
kind
of
most
important
things
that
we
should
discuss.
A
First,
which
are
any
data
from
compounds
that
we
hope
to
be
multi-targeting,
either
from
the
working
uni
collection
or
the
atom
y
set.
Then
what
I
think
we
need
to
talk
about
some
data
on
you
hangs
redesign.
Well,
derivatives
of
of
the
AZ
Mercy
inhibitors
and
the
implication
of
those
data
on
what
we
need
to
be
doing
next
and
there's
been
a
really
productive
conversation
going
on
between
you,
hang
and
Joe
offline
about
that,
and
then
any
other
data
on
those
two
sides
of
the
project.
A
I
think
are
the
are
the
key
things
and
then
we
can
raise
any
other
business,
I
guess
so,
I,
don't
know
which
way
you
want
to
do
this.
The
Warwick
team,
I
I,
saw
you
posted
some
data.
Just
before
the
meeting
did
you
want
to
present
something
or
first
up
just
to
get
us
going.
C
I
think
first
risket
is
going
to
clear
up
the
conundrum
about
Compound
W.
Okay,
there
isn't
a
big
problem
here.
It
was
me
simply
mislabeling
barcode,
1093342664.
C
Which
is
664
as
Compound
W,
it
is
not
Compound
W,
so
I
I
missed
that
I
just
thought.
Oh
that's
Compound
W!
We
actually
have
not
had
the
AZ
compound
four
here
at
all,
so
all
we've
ever
had
is
uhans
Compound
W,
which
is
a
z
compound
four,
whatever
AZ
compound
four,
as
you
can.
D
Okay,
so
so
so
or
you
got
so
so
the
first
first
two
curves
was
from
was
from
compound
four,
then
so.
C
All
the
we
don't,
we
don't
have
any
compound
four
okay,
we
don't
have
anything
called
compound
four
here.
All
we
have
is
your
Compound
W
and
wyh9.
That's
all
yeah!
So.
D
So
the
so
all
the
so
about
the
about
the
curves
about
the
inhibition
data
you
guys
presented
yeah
yeah,
so
here
so
in
in
that
file.
These
four,
these
four
pictures
were
actually
from
this
Compound
W
yeah
all
right.
So
it's
not
from
the
successful.
C
E
D
Oh,
so,
by
the
way
so
about
the
about
the
deviation
about
the
data
isa50
of
this
Compound
W
against
the
pseudonymous
original
Mercy
I
found
it
was
1.2
micro,
molar
and
according
to
the
literature,
was
Anonymous
scale.
I
think
is
that
is
there
is
there?
Is
there
a
reason
for
such
a
huge
division?
D
E
E
So
if
you
put
a
really
tight
lining
inhibitor,
which
for
which
the
enzyme
actually
acts
like
a
mop,
the
ic50
will
approach
something
like
half
the
enzyme
concentration
in
the
assay.
Now
with
some
of
the
particularly
the
most
crcs,
we've
done
with
Hunter
use
fairly
high
enzyme
concentrations
to
get
decent
rates
that
we
can
measure
inhibition
against,
and
so
that
will
noticeably
have
an
impact
upon
the
range
of
ic50s.
We
can
go
down
to.
C
So
I
don't
think
it's
anything
to
worry
about.
Thanks.
A
I
mean
certainly
on
the
numbering
here,
having
so
many
codes
for
one
molecule,
there's
sub-optimal
obviously,
and
we're
going
to
get
confusion
if
we're
not
careful,
so
we've
been
using
Compound
W,
but
the
these
codes
are
uhang's
internal
codes.
These
AZ
compound
codes
are
the
ones
that
they
use
in
the
Hamid
paper,
and
the
Osa
code
is
the
one
that
you
use
for
the
whole
project.
I
think
we
should.
A
We
should
try
and
be
consistent
about
what
we're
using
generally
speaking,
because
we
also
tend
to
add
in
commercial
codes
as
well
to
to
the
mix
here
and
we've
just
got
to
be
careful
not
getting
confused.
A
Right
was
there
anything
else
you
wanted
to
ask
about
this
issue,
or
do
you
think
that's
resolved.
D
I
think
it's
resolved
thanks
thanks.
Everyone,
okay.
A
E
E
A
B
E
All
right,
so
we
got
sent
last
year
overrated
compounds
that
were
the
basis
of
the
competition
the
UCL
held
in
order
to
generate
novel
Inhibitors
of
murti,
and
we
screened
them
and
we
screened
them
using
the
fluorescent
assay
that
we've
been
using
thus
far,
and
what
became
fairly
apparent
is
that,
on
the
face
of
it,
a
large
number
of
these
compounds
were
actually
active.
E
It
in
more
detail-
and
we
looked
at
the
company
enzymes,
which
we
use
to
detect
the
products
of
the
Murdy
reaction.
We
found
that
the
coupling
system,
the
desertion
system,
was
also
subject
to
Marta
inhibition
by
these
compounds.
So
the
coupling
system
we
use
in
the
fluorescent
assay
involves
read
proteins
so
pure
nucleoside,
phosphorylase,
PMP,
xanthinoxidase
and
all
strategic
peroxidase.
And
if
you
like,
those
are
three
liabilities
with
regard
to
interference.
E
E
E
And
they,
both
on
the
face
of
it,
give
complete
inhibition
at
0.5,
millimolar,
I've
reactionate.
Those
compounds
against
the
coupling
system,
which
now
is
a
lot
simpler,
is
the
single
enzyme,
and
it
turns
out
that
I'm
very
confident
that
Osa
double
zero
triple
one.
Zero
is
emerging
inhibitor
which
we're
going
to
be
taking
forward
into
ic50s.
E
E
A
Very
interesting:
we
need
to
correlate
whether
or
not
the
one
that's
binding.
There
is
the
one
that
Bound
by
was
was
found
Divine
by
spr,
because
that
was
the
result
that
we
had
previously
that
one
of
them
gave
something.
A
It
would
be
amazing,
of
course,
if
that
was
the
same
compound
yeah,
but
we
will
have
to
do
that.
Correlation
great
I
mean
that's
very
interesting.
We
will
I
mean
so.
Ultimately,
yes,
if,
if
you
are
able
to
generate
ic50s
for
maybe
both
of
those
definitely
the
one
on
the
right,
maybe
both
then
we
do
I
mean
we
need
to
be
trying
to
publish
this
well,
because
we
we
had
contributions
from
lots
of
people
and
it'd
be
great
to
reward
those
contributions.
A
Given
that
we've
gone
and
got
the
compounds
and
now
evaluated
them
so
I
guess
we
need
to
just
get
to
a
point
where
we
think
we've
identified
something.
That's
concrete
and
useful,
so
I
mean
just
bear
that
in
mind
that
ultimately,
here
it's
a
it's
a
it's.
A
this
set
of
compounds
is
separate
from
everything
else
we're
doing
and
we
can
publish
it
independently.
Yes,.
C
And
my
memory
fails
me
as
opposed
to
these
days
and
we
haven't.
We
have
a
list
of
that
must
have
a
list
of
those
structures
shared.
A
C
C
All
right,
okay,
we'll
we'll
we'll
keep
looking
see
if
there's
any
SBR
correlation
yeah.
E
Anything
else
there
is
any
mean
news,
but
I've
really
got
to
collect
the
data
before
I
want
to
present
it
more
properly.
But
essentially,
we've
worked
everything
down
to
18
compounds
how
I
got
there
is
something
I'll,
let
you
know
one
once
I've
compiled
everything,
but
there
are
18
compounds
now
which
require
one
final
screen
with
the
coupling
system,
rather
than
like
I've
done
here
and
ic50s,
but
there
will
be
more
to
follow.
But
if
you
don't
mind,
I'll
get
the
data
collated.
First.
B
B
Oh
just
so
a
single
isozyme
yeah
and
you
have
and
you've
tested
those
against
other
isozymes
or
just
your
D.
At
this
point,
that's
fine
I
mean
I,
know
you
I
know
just
just
curious
in
the
sense
of
you
know
how
many
compound
or
how
many
of
the
isosimes
have
been
actually
been
tested
against
the
polynomial
Library.
E
Against
the
following,
the
main
library,
d
and
e
against
the
hits
screen
yielded
pseudomonas
d
and
e
against
the
full
Library
D,
with
the
intention
to
go
on
to
do
the
coli
d
and
e
at
the
moment
anyway,.
C
So
the
discussion
was
whether
to
just
do
the
ic50s
first
and
then
take
the
best
of
those
and
then
screen
those
against
the
other
isosomes
or
take
the
hits
and
scream
all
the
isosomes
and
then
choose
those
that
hit
the
most
isocytes.
Do
the
xc50
I
mean
we
had
those
discussions
that
we
decided
to
do
the
ic50.
E
B
F
E
B
F
D
I
I
can't
find
any
ligands
from
the
soaking
experiments,
but
I
also
did
new
caucus
transition.
Experiments.
A
different
compound
concentrations
and
they've
got
a
new
Crystal
for
E
coli
near
the
on
the
compound.
Dr6
and
I
have
optimized
it
and
I'm
sending
it
to
time
on
tomorrow.
F
So
let's
hope,
let's
hope
the
crystal
looks
different
from
any
other
crystals
that
I've
been
getting
from
UD.
So
I
have
physically
hopes
on
that
yeah
and
hopefully,
but
it's
been
a
lot,
a
lot
of
failure
structures
so.
C
I
think
the
bottom
line
is
that
e
Carolina
D
doesn't
work
as
a
stoking
system.
You
put
them
in
you,
get
changes,
but
there's
no
struct,
there's
no
code
structures.
Yeah,
you
just
lost,
you
know
the
the
things
start
flexing
and,
and
the
compounds
are
spat
out.
Basically,
whereas
so
there's
this
this,
the
the
co-crystallization
we've
got
a
completely
different
morphology
from
APO.
So
the
finger
crossed
actually
that
it's
a
co-structure.
F
F
F
Not
it's
not
going
to
work
for
these
enzyme.
No
new
e
I'm
still
having
the
issues
with
the
reproducibility
because
of
their
robot.
There
are
some
issues
with
the
robot
and
new
Acres
that
are
really
sensitive
to
any
changes.
Basically,
so
they
were
not
good
enough
to
do
proper
soaking
on
them.
Yeah.
It's
not
a
soccer
ball
system,
but
I'm
a
bit
hopeful
with
the
caucuses
at
least
we're
getting
something
new
that
I
never
gotten
before.
F
These
crystals
had
never
got
an
important
before,
but
these
are
a
problem
with
these
compounds
because
I
need
them
are
really
high
concentration
for
like
crystallization
conditions,
but
you
cannot
go
to
really
high
constructions
because
they
are
not
that
soluble.
So
it's
a
balanced
but
I'll,
let
you
know,
usually
they
give
me
beam
time
really.
F
A
Really
good
all
right
just
on
the
same
subject,
then
we
just
wanted
to
update
everyone
on
the
compounds
that
are
being
made
so.
B
G
Yeah
Scott
Scott
Lovell
at
Kansas,
University
or.
G
B
I
was
just
at
one
point
we're
talking
about
sending
compounds
to
him
for
Crystal
work
and
I.
Don't
know
what
is
the
status
of
that.
G
Yes,
guts,
working
away,
I
apologize,
I,
don't
have
a
specific
update
on
the
the
the
j06
crystallizations
like.
B
A
It
would
be
very,
very
useful
just
to
have
a
couple
of
lines
in
an
email
about
about
what
he's
looking
at
just
so
we're
all
on
the
same
page.
If
you
can
I
mean,
and
we
can,
we
can
share
it
on
the
site.
But
if,
if
something
could
be
relayed
about
about
what
he's
got
and
what
he's
looking
at
that'd
be
very
interesting.
Okay,
because
I
admitted
that
I've
forgotten
to
what
the
status
of
that
one.
A
Okay,
good
thanks
and
then
so
yeah,
just
a
quick
update
on
compounds
that
are
going
to
be
sent
or
or
well
no
going
to
be
sent
pretty
pretty
soon,
I
think
so
these
from
the
from
the
search
of
commercially
available
analogs
of
the
compounds
which
appeared
to
be
giving
some
multi-targeting
behavior.
A
These
were
the
compounds
that
were
purchased
by
Ed
and
they're,
currently
sitting
in
the
fridge
or
freezer
in
in
our
lab
at
UCL,
and
we
were
just
waiting
to
check
that
they
could
be
received
and
evaluated,
because
these
are
the
ones
that
are
surrounding
the
compounds
that
we
we
found
interesting.
These
are
the
most
similar
compounds,
energy
check
that
we're
not
doing
The
Singletons
and
everything
so
they're
they're
ready
to
go
and
we
were
just
waiting
for
a
couple
of
competition
compounds.
A
A
If,
if
those
can
be
evaluated
because
that's
all
of
them
and
then
the
last
group
that's
coming
through
were
ones
that
were
not
commercially
available,
and
so
these
compounds
are
being
made
by
Yi
Wei
who's
on
the
call
and
is
doing
a
master's
project
in
the
lab
at
the
moment
and
Eve
Carter
who's
a
postdoc
in
the
lab
who's.
He
was
working
on
something
else,
but
the
chemistry
is
a
little
quiet
at
the
moment.
A
So
she
she
made
a
few
analogs
of
aw9
just
to
play
around
with
the
structure
a
little
bit,
so
the
red
ones
are
ready
to
go
and
the
orange
ones
I
think
I'll
be
ready
by
the
end
of
the
week.
So
we
can
ship
all
those
off,
probably
on
Friday
to
our
evaluation.
C
A
Okay,
there
was
one
other
company,
so
so
that's
the
aw9
and
aw53
and
my
memory
is
going
to
tell
me.
A
Well,
no
I
mean
I
think
these
are
the
multi-targeting
ones.
Oh
sorry,
the
competition
compounds
yes,
but
these
ones
were
derived
from
the
multi-targeting
hits
and
and
what
they
hit
is
up
yeah
as
a
reminder.
So
you
will.
You
will
have
a
better
sense
of
an
eye
about
what
they
should
be
evaluated
against.
C
B
A
J06,
though,
was
not
on
here
and
I
promised
I,
wouldn't
ask
to
say
anything
on
the
call
because
he's
feeling
sick,
but
there
was
another
set
of
compounds
that
I
think
we
were
thinking
about
that
were
around
js6,
but
I've
forgotten
what
that
is,
and
if
you
don't
want
to
contribute
to
the
audio.
You
can
just
put
a
comment
on
the
on
the
GitHub
issue
about
what
we
were
doing
about
the
last
set
of
compounds
around
js6,
because
I
think
there
was
one
more.
H
I
think
I
think
you
can
see
it
in
the
multi-targeting
issue.
I
think
I
started
working
on
it,
but
didn't
manage
to
finish
it.
G
H
H
D
H
A
Similar
to
j06
is
pretty
low,
so
that's
all
that's
available.
Basically,
so
yeah
it'd
be
nice
to
be
able
to
make
js6
and
then
be
able
to
vary
it.
If
we
find
the
compound
interesting.
So
we
do
have
a
synthetic
plan
and
it
started
it,
but
yeah
we
can.
We
can
look
that
again.
I
guess
this
j6.
It
becomes
increasingly
interesting.
A
Okay,
great
thanks
Ed,
so
yeah
those
will
be
winging
their
way
to
you
pretty
soon,
hopefully
on
Friday.
That's
the
idea.
Okay,
okay!
Does
anybody
else
have
any
questions
about
the
the
war
against
me
collection
or
will
the
atomized
compounds
and
this
multi-targeting
compounds
for
those
sets
that
we
have
been
looking
at.
A
Okay,
if
not,
then
we
were
then
going
to
move
on
to
some
data
on.
A
Of
the
AZ
compounds
so
the
the
set
that
was
found
by
Hazard
a
few
years
ago
and
as
I
think
everyone
knows,
don't
have
the
structures
right
here,
but
structures
of
this
kind
were
were
of
interest
and
euhan
was
changing
this
oh
to
an
nh2,
to
try
and
improve
it's
the
compound's
ability
to
accumulate
those
compounds
found
no
particularly
good
potency
against
wild
type
bacteria,
and
we
were
hoping
to
get
data
on
whether
or
not
the
compounds
were
inhibiting
the
enzymes
in
vitro
just
so
that
we
know
whether
or
not
the
design
itself
is
okay
or
not
so
just
to
sort
of
close
off
that
part
of
the
the
project
and
I
think
some
data
has
been
has
been
coming
in
I
paced,
the
Sun
that
came
in
through
email,
which
was
this
compound
over
this
was
wa
H9,
which
is
I.
D
A
A
Right,
yeah,
okay
and
then
so
the
question
was
you
know
whether
or
not
these
compounds
have
you
hang
sort
of
the
aiming
derivatives
inhibit
the
enzyme.
Does
anybody
want
to
update
us
if
we
have
data
in
that
area.
F
C
So
so
you
it'll,
be
a
you
hand,
you
hand
table.
A
Yes,
did
you
have
that
table
of
data
to
hand
the
the
table
that
you've
got?
That
summarizes
the
data
against
your
compounds?
Oh.
C
D
My
company,
oh
on
the
Wiki
page,
let
me
share
the
screen.
A
A
Right
but
but
I
thought
you
also
had
columns,
which
were
talking
about
whether
or
not
you've
got
ic50
data
again
specific
enzyme.
Oh.
A
C
A
Think
wait.
Let
me
just
get
rid
of
that.
So
I
think
we've
got
the
the
issue
was
that
we
needed
sorry.
Forgive
me
what
is
it
we're
looking
for?
We
need
to
know
yeah
whether
or
not
these
things
are
in.
A
C
Anita's
on
another
job
at
the
moment,
she's
training
some
folk
in
the
micro
lab,
which
is
why
she's
not
here
otherwise
she'll,
be
able
to
tell
us
whether
she's
done
those.
Let's
all
my
emails
from
her
okay,
because
the.
A
Next
step
here
is
for
you,
Hank's
PhD
is
to
is
to
finish
off
that
little
bit
of
the
project.
But
then,
if
the
design
is
basically
okay,
then
there
are
other
things
that
he
can
do
in,
rather
than
just
having
a
primary
aiming
on
the
molecule.
There
are
a
couple
of
other
things
that
can
be
done,
which
are
thought
to
improve
accumulation
like
pyridinium
ions,
and
things
like
that,
which
makes
sense
to
look
at
while
he's
doing
this.
A
C
That's
you
know
it's
the
derivatives.
We
need
to
go
and
check.
A
Then,
beyond
that,
beyond
the
the
tinkering
with
the
compounds,
you
hang
and
Joe
have
been
corresponding
about
a
more
fundamental
redesign
of
the
molecules
based
on
what
we
know
of
how
they
bind,
which
has
been
really
productive.
And
we've
done
this
in
part
because
you
haven't
got
a
plan
ahead
and
in
part
because,
as
we've
discussed
before,
we
wanted
to
try
to
ask
cc4
carp
for
some
chemistry
inputs,
and
so
we
were
trying
to
think
about.
A
Well,
you
know:
is
there
a
set
of
molecules
that
you
had
could
usually
make
which
are
coherent
and
self-contained,
and
then
another
set
of
molecules
that
we
could
go
to
CC
for
carb,
with
some
strong
justification
to
make?
You
know
so
more
of
a
structure,
guided
approach
and
I.
Guess
they've
been
talking
a
lot
about
this
and
come
up
with
some
really
good
ideas
and-
and
we
don't
really
have
time
to
go
through
them
all
now,
but
did
you
want
to?
Did
you
want
to
summarize
the
the
basic
conclusions.
D
From
that,
I
can
share
the
one
slice
for
you.
If
you
want.
A
D
Zooming,
so
this
is
the
this
is
a
basic
design,
we've
done
with
Joe
and
Yeah.
So
basically,
we
are
we're
focusing
on
modifying
this
structure
of
the
az595.
We
have
several
plans.
We
decided
to
cut
this
bit
cut
this
big
group
off,
because
it
has
the
potential
risk
of
Clash
of
historical
clashing
with
the
with
the
c
terminus.
D
D
So
that's
what
we
are
trying
to
do,
and,
according
and
based
on
this
design
rationale,
I
decided
to
pick
up
the
superzollo
pyramiding
core
still
and
the
other
one
and
the
other
one
is
the
Purity
Purity
Amy
as
a
core
for
my
next
stage
of
PhD.
This
is
just
basically
the
scaffold
ask
or
the
scaffold
hopping.
D
The
other
three
cores
I've
designed
was
for
the
cc4
cup
and
one
one
thing
worth
mentioning
here
is
you
can
see
this
missile
Amy
group
here
or
the
essential
group
here?
These
two
groups
are
pretty
much.
D
These
two
groups
are
pretty
much
design
or
designed
here
because
we're
expecting
to
have
extra
interactions
in
the
in
the
pocket
and
then
we
then
we
then
I
decided
to
do
a
little
bit
of
a
balance
of
stereo
replacement
or
either
position
one
or
position
two
just
to
make
sure
the
these
Pockets
have
been
explored.
So
to
know
the
details
of
the
design
are
so
I.
Basically
did
the
constraint
constraint
docking
using
this
structure
with
the
of
the
ultra
soliding
yeah.
D
It
was
just
random
thoughts.
I
thought
this
one
could
be
could
be
long
enough
and
as
the
ADP
and
the
potential
risk
that
beta
Helix.
Oh
sorry,
sorry,
not
the
Helix
residues
and
luckily
I
found
okay.
These
these.
This
carbonyl
group
was
actually
having
the
interactions
with
the
with
the
residues
where
we
would
like
to
Target
home
and
therefore
I
decided.
D
Okay,
I
cut
this
big
big
stuff
off,
because
it's
basically
nothing
and
then
add
a
little
bit
more
flavor
on
it
on
it
like
adding
a
carbonyl
or
something
else
whatever.
It
also
has
the
interactions.
So
basically,
this
we
decided
to
so
I
just.
A
I
did
a
whole
photo
one
sec,
just
one
sec.
Can
you
just
go
back
to
sleep
so
just
to
take
a
step
back
in
terms
of
the
the
change
to
the
structure
here
for
for
the
biologists
amongst
us,
the
chemistry,
the
bit?
A
The
big
difference
here
about
where
the
molecules
being
varied
is
that
in
the
structure
on
the
top
right,
the
kind
of
red
nh2
is
what
you
hang
has
so
far
been
experimenting
with
to
try
and
change
that
into
a
group
that
would
still
bind
but
would
improve
accumulation
and
the
key
Insight
that
that
Joe
came
along
with
was
that.
A
Well,
if
you
look
at
the
structures,
then
growing
the
top
right
of
the
structure
up
to
meet
other
parts
of
the
protein,
as
shown
on
the
left
would
be,
would
be
really
quite
productive
in
the
sense
that
there
nothing
much
has
been
done
there.
You
know
the
previous
structures
that
we've
had
have
had
a
hydrocarbon
group
there,
basically
which
isn't
really
making
many
useful
interactions
with
the
protein.
So
so
that's
the
real
difference
here.
It's
a
different
part
of
the
molecule
that
is
being
grown.
A
B
So
I
think
the
the
main
yeah.
So
if
you
look
at
the
structure
of
the
I
guess
this,
what
do
you
have
here?
You
have
a
oxazolezone.
It
looks
like
there
in
the
upper
right,
so
this
is
all
this
is
I
mean
you
don't
have
I,
guess
a
good
overlay
with
ATP,
but
this
is
where
the
phosphates
of
ATP.
So
these
compounds
are
much
more
staying
in
the
same
shape
as
ATP
or
ADP.
B
That's
what
we're
trying
to
most
for
the
most
part
trying
to
keep
these
Inhibitors
in
the
same
occupying
the
same
space
as
substrate,
so
these
are
not
going
so
in
theory.
In
theory,
these
should
be.
You
know,
less
susceptible,
for
example,
to
The
c-terminal
Domain,
because
they're,
basically
occupying
the
same
spaces,
ADP
ATP,.
D
D
A
D
Oh
no,
so
so,
based
on
these
these
ideas,
so
we
designed
a
whole
list
of
what
I
would
like
to
make.
This
is
cluster
one
which
is
the
which
is
the
first,
which
is
the
position
one
being
explored
because
the
position
one
is
a
relatively
facing
toward
the
internal
side.
So
the
space
we
could
do
modifications
will
be
smaller,
so
we
don't
want
to
start
stuff
it
a
really
big,
a
really
big
group
into
it.
D
So
I
kind
of
make
it
a
little
bit
smaller
and
varying
different
cores.
Those
ones
are
relatively
difficult
to
make
for
for
64
cards.
Sorry,
one
yeah
and
the
class
of
two
is
basically
the
same
idea.
These
are
these
sort
of
variations
we
want
to
explore
for
for
my
project
and
for
ceaseful
carved.
We
have
even
more
on
the
position.
Two.
If
you
guys
want
to
look
at
I,
can
zoom
in
no.
A
That's
all
good
I
think
I
mean
the
point
here
is
really
that
we
wanted
to
give
something
self-contained
and
different
for
cc4
carb
with
a
strong
justification.
So
so
so
you
know
the
the
general
outline
of
the
structure
and
then
and
then
we
will
propose,
you
know
10
compounds
or
something
yeah
that
think
are
accessible
and
then
go
with
them.
Go
to
them
with
that
proposal,
making
it
clear
that
the
compounds
are
different
from
the
one
that
ukang's
already
making
so
that
this
yeah
there's
a
line
between.
B
B
More
likely,
you
know
additional
design
and
input
into
whatever
kind
of
Library
would
get
made.
Yeah
I
was
hoping
for
that.
Actually
I
was
hoping
it.
No,
no
that
yeah
anyway
yeah
so
I
wouldn't
get
you
know,
I
wouldn't
get
too
worried
about.
You
know
having
you
know
a
big
full.
You
know
expanded
set
because
they're
gonna
probably
have
their
own
input
and
thoughts
on
how
to
go
things.
So,
okay,
it's
more
the
concept,
yeah.
C
Cool,
if
you
want
to
get
back
to
you
and
compounds
we've
we've
mailed
out
several
to
several
people,
including
Johan,
the
fact
that
we've
actually
tested
wh,
six,
nine
fifteen
Seventeen,
twenty
two
and
twenty
five
against
a
range
of
isoz
for
inhibition,
so
I
think
u.n's
not
only
Scott
those.
So
that's,
Super,
C,
E
coli
mirror
D
pseudomonas.
C
C
Yeah
I'm
just
saying
that
we
have
done
the
Innovation
stuff,
so
we
know
which
ones
to
to
go
for
if
you
want
to
come
Joe
and
spend
a
month
or
two
doing
some
ic50s
with
us
you'll
be
very
welcome.
A
All
right,
that's
good!
Those
are
the
most
important
things,
I
think
from
my
perspective,
anybody
else
want
to
raise
anything.
F
The
competition
compounds
there
is
not
a
great
correlation
between
the
essays
and
the
SBR
data
so
for
the
company
that
was
the
best
one
on
the
essays
and
I
couldn't
calculate
a
KD.
It
was
just
showing
me
a
KD
greater
than
500
macamola.
F
But
again
the
systems
are
completely
different.
I'm,
not
I,
don't
have
any
compound
any
substrates
or
ATP,
or
things
like
that
on.
The
sprsa
is
April
product.
G
F
F
Because
it
would
be
I,
don't
know
how
we
are
gonna
make
so
much
this
trade
into
able
to
do
a
one
with
assist
trade
because
they're
running
buffer,
you
use
a
lot
of
buffer
and
you
wouldn't
disconline
the
running
buffer.
If
we
had
a
different
SPI
instrument,
it
would
be
a
different
story,
but
will
we
can
access
this
at
the
moment?
We
will
need
a
lot
of
volume,
which
means
a
lot
of
milligrams
or
grams
of
this
a
straight,
and
we
can't
Supply
that
right,
right,
yeah,
that's
the
limitation
at
the
moment,
so.
B
These
are
all
so.
These
are
all
meant
to
be
ATP
competitive.
So
why
can't
you
use
simpler,
ATP
analog.
F
F
E
F
Street
reference
instructions
at
every
single
point:
yeah.
He
uses
a
lot
of
buffer.
B
F
No,
no,
nothing
so
the
the
meal
ideas
is
not
the
limited
step.
In
this
case,
it
would
be
if
we
want
to
do
the
screening
on
SBR
in
the
presence
of
any
of
the
substrate
or
cofactors.
F
That
would
be
the
limiting
factor,
disaster
or
difficult
Factor.
The
protein.
We
don't
need
much
protein.
C
A
A
F
Yeah,
so
it
will
have
to
be,
and
from
ADP
and
a
PNP
PCP
was
the
best
one.
F
F
A
F
F
C
C
A
F
Assets
we
see
seems
to
be
picking
up
so
many
heat
leaders
as
well
yeah,
which
is
good
so.
E
I
guess
there
are
other
things
we
can
do
as
well.
We
can,
if
we
get
lucky
in
the
protein
fluorescence
changes
with
compounding
of
some
of
these
things
that
might
be
a
workaround
towards
getting
equivalent
data.
E
Is
that
that's
something
that
we'll
have
to
think
about
and
try
and
work
out?
Thank.
C
A
Okay,
great
thanks,
it's
very
useful
anything
else
before
we
go
I
think
we'll
we'll
park
the
discussion
of
the
predicted
compounds
from
Yan
yansen.
You
hang
because
I
know
you're
working
on
those,
but
we
can
wait
until
he's
at
the
meeting
and
until
you
finish
the
first
batch
all
right.
If
there's
nothing
else,
then
we
can
call
it
a
day
thanks
very
much
for
coming
along
anything
else.
You
want
to
add
just
please
put
it
on
the
get
obsc.
Obviously,
as
usual,.