►
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/94
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
And
so
there
are
the
usual
things
here
but
I.
You
know
again
I'd
like
to
focus
in
on
a
few
key
things
initially
and
then,
and
then
we
can,
you
know,
call
for
any
other
business
or
anyone
to
present
their
ass
and
presented
here.
I
guess.
For
me,
the
the
main
thing
is
is
to
get
a
an
update
on
the
the.
A
So
just
while
we're
while
we're
on
that,
while
I
had
the
floor,
there
was
an
update.
Oh
actually,
it
was
it's
already
I.
Think
Ed
has
already
posted
it
to
the
issue
just
now.
So
let
me
just
reshare
that
sorry,
so
the
I
guess
we
wanted
to
update
everyone
and
make
sure
everyone
was
aware
of
what
we've
been
buying
here.
A
These
are
a
little
bit.
It's
a
little
bit,
that's
better!
These
are
compounds
that
are
so.
The
compounds
that
we
know
about
are
up
top
there,
the
the
compass
that
gave
promising
data
in
terms
of
multi-targeting-
and
these
are
the
ones
that
we
found-
that
there
were
commercial
commercially
available
components,
also
inexpensive
molecules
and
have
these
all
now
come
in.
A
A
It
would
be
really
useful
if
we
could
keep
some.
So
that's
why
we're
asking
Laura
about
how
you
want
us
to
send
these
compounds.
We
can
make
up
DMSO
stocks,
but
of
the
sort
of
five
milligrams
or
so
I.
Think
it's
about
five
milligrams
of
each
that
we've
got.
We
would
love
to
keep
some.
You
know
as
as
part
of
our
group
compound
Library,
basically
yeah,
so
we
can
fix
that
up
and
send
you
enough
for
you
to
do
the
analysis
with
if
we
could
just
keep
something
yeah.
A
It's
it's
so
we're
talking
with
lots
of
different
people
about
how
best
to
store
compounds
in
a
compound
Library,
that's
useful
and
and
the
two
other
places
we're
talking
to
are
Frankfurt
in
Toronto,
because
they're
SVC
sites
and
they
both
have
different
concentrations
in
DMSO.
You
know:
10
millimeter,
20,
millimeter,
you're,
the
you're,
the
highest
concentration,
so
we're
not
going
to
be
able
to
you
know
satisfy
everybody,
but
I,
guess
the
more
concentrated
the
better
provided.
A
A
D
D
A
D
A
Great
great
I
mean
with
these
tested
these
last
two,
then
that's,
that's
all.
Essentially,
that's
all
the
composition
compounds
right
so
I
mean
we
should
take
stock
of
the
data
when
we
have
the
data
and
and
and
see.
What's
what
in
terms
of
writing
it
up,
because
you
know,
if
we
found
a
binder
and
it's
it's
real,
then
it
would
be
nice,
a
nice
little
paper
on
generative
modeling.
A
A
Okay,
we
can
have
a
look
at
offline,
but
I
guess
we
because
Daniel
was
going
to
do
it,
but
then
he
finished
up
all
right,
great,
so
just
to
flag
up
that
these
are
the
this
chemistry
is
being
sorted
out
with
the
view
to
making
a
few
derivatives,
because
these
were
not
simply
commercially
available
and
these
ones
are
ready
to
go.
So
it's
it's
pretty
easy
to
generate.
You
know,
compounds
quickly
for
this
kind
of
work,
all
right.
A
So
that's
the
sort
of
chemistry
that's
been
going
on
in
the
lab,
related
to
the
the
enemy
and
or
a
collection.
I
guess
that's
a
segue
into
you
know
Warwick
any
work
updates
on
those
compounds
in
terms
of
potentially
getting
structures
from
any
of
the
multi-targeting
compounds.
Who
is
now
a
good
time
to
talk
about
that.
A
E
Yeah
well,
I
haven't
been
able
to
get
again
everything
working,
so
I'm
working
on
that,
so
I
don't
have
updates
on.
On
that
end,
okay
and
yeah
we
said
initially
to
send
as
well
to
the
ssgc
ID
the
year.
6
compound
this
is
to
be
seems
to
be
one
of
the
top
compounds
for,
for
the
from
the
end,
I
mean
so
I
need
to
get
to
the
sscc
Edition.
They
can
also
try
with
whatever
enzymes
they
have
a
Bible.
At
the
moment.
E
Looking
at
the
essay
data
prioritizing
with
the
essay
data
we
might
have
a
potentially
another,
one
is
mo2
that
we
could
also
send
yeah.
They
are
again
they
are.
You
know
we
are
not
talking
about
the
best
Inhibitors
yet
because
they're
macromole
Inhibitors,
but
we
could
give
it
a
try
as
well
with
their
system.
A
E
C
G
Good
Okay,
so
I
haven't,
talked
to
support
some
of
the
writing
going
on
about
NIH
proposal
and
also
to
catch
up
on
some
of
the
compounds
that
came
out
as
hits
from
the
enemies
scream
and
also
because
we've
had
an
issue
whereby
we
now
are
in
the
market
for
another
Plate
Reader,
because
one
of
the
ones
we're
using
the
one
I
used
to
use
is
broken
down.
So
I've
had
to
train
myself
on
another
and
what
we've
done.
G
So
what
we're
doing
from
now
on
is
we're
going
to
be
doing
all
the
High
throughput
Library
wide
screening,
with
the
fluorescent
assay
we
developed
and
re-screening
those
hits
with
this
second
assay
just
to
triage
out
anything
that
turns
out
to
be
spurious.
So
with
that
second
Becca's
assay,
it
behaves
very
well.
We
get
nice
ic50s
if
we're
talking
about
economy
and
if
we're
talking
about
e
Carolina
e
and
hits
apart
from
j06.
G
But
the
one
good
thing
about
this
is
actually
the
data
itself
in
that
it
shows
a
very
nice
hyperbolic,
smooth
response.
You
would
imagine
that
it
can
be
represented
by
one
bonding
constant
and
that
actually
is
what
we're
looking
for
foreign.
Occasionally,
however,
we
don't
see
that
so
another
hit
is
f09,
where
the
relationship
between
concentration
and,
in
addition
is
a
little
bit
more
animatic.
G
We
see
if
the
higher
concentrations
precipitation-
and
we
really
can't
make
any
sense
of
that,
so
we've
gone
through
f09
and
mo2,
not
just
with
E
coli,
Mur
e,
but
also
with
d
and
in
the
case
of
Modi.
We
see
a
sigmoid
response
as
opposed
to
a
hyperbolic
one
which
might
suggest
for
this
particular
protein,
there's
more
than
one
binding
interaction
going
on
and
similarly
with
f09
again
there's
more
than
one
interaction.
G
So
f09
with
respect
to
the
compound
to
the
enzymes,
we're
working
with
I
would
say
it's
not
something
we
would
readily
follow
up
simply
because
we've
got
considerably
more
than
the
single
interaction
going
on
it's
rather
more
complex.
Finally,
We've
also
looked
at
pseudomonas
original
C
with
respect
to
mo2.
G
Again
we
we
get
a
sigmoid
response
with
an
ic50
of
about
490..
So
at
the
moment,
in
addition
to
supporting
the
NIH
Grant,
we're
basically
plowing
through
the
other
enamine
hits.
We've
got
with
this
second
assay
and
then
the
idea
is
to
go
on
and
do
the
ic50s
that
come
out
of
those
compounds
which
give
attractive
looking
Behavior
with
respect
to
their
responses
to
inhibitor,
and
that's
really
where
we
are.
C
C
G
C
G
E
G
G
E
A
E
E
A
E
G
G
C
E
G
A
B
C
H
B
Yes,
Scott's
gun.
What
we're
doing
right
now
with
ssgcad
is
the
the
lab
in
Kansas
is
going
to
be
doing
the
crystallizations
and
they
have
a
nice
robotic
setup
that
does
small
drops
as
well
as
they
just
got
a
new
like
Crystal
Rock
Hotel
that
they're
really
enjoying
putting
things
in
and
scanning
all
the
time.
B
C
G
Yeah,
no
I
can
appreciate
that
because
they
well,
they
all
fragments
they
bond
Weekly
right.
Exactly
one
thing,
I
was
going
to
say:
if
you,
if
the
activity
is
a
question,
should
the
the
enzymatic
activity,
if
you
send
us
a
protein
sample
or
samples,
we
can
very
quickly
in
short
or
to
tell
you
whether
they're
active
or
not,
if
that's
actually
something
that's
useful.
B
Yeah
I,
that
sounds
that
sounds
great
I,
think
that
some
it's
often
useful
to
know
that,
because
it's
sort
of
it
it
helps
us
kind
of
gauge
our
effort
level
right.
You
know
we
might.
We
can
set
up
the
crystal
trials
pretty
easily
and
watch
them.
You
know
there's
just
a
couple
of
Crystal
trials,
but
if
we
actually
have
you
know
if
we
but
then
are
we
gonna
set
up
like
thousands
of
Trials,
probably
not
we'll,
probably
set
up
the
standard
short
screen
and
then
and
see
what
happens?
H
So
I
think
only
I
mean
from
my
side
I
think
the
focus
should
just
be
on
j06
and
as
many
of
the
mirror
ligases
that
you
can
screen
against
with
j06,
and
you
know,
since
the
potency
of
that
is
centrically
below
50
micro
mower
I
mean
in
terms
of
DMS
low
concentration,
you
shouldn't
have
to
be
at
a
real
high
DMSO
concentration,
I,
wouldn't
think
m02,
yes,
but
but
I
mean
I.
Think
it's
a
focus.
G
H
B
C
G
B
A
E
F
F
F
F
You
play
yeah,
so
I
think
that's
our
plan
and
and
knowing
that
there.
Hopefully,
if
there's
some
more
successful
in
more
chemistry,
then
we
can
justify
pushing
pushing
that
forward
as
well
to
the
you
know:
Brave
New
Day,
when
hopefully
we
can
put
in
for
some
multi-million
Bank
Grant
to
really
make
it
joint
jointly
work
together
for
everybody.
A
F
A
The
data
that
came
back
on
the
uhangs
e-flux
proof
aiming
which
I'm
not
sure
we
talked
about
last
time,
but
so
the
the
derivative
of
the
Azo
compound
5595
and
you
hang
made
the
amino
derivative
of
that
as
a
as
a
way
of
trying
to
reduce
efox,
but
that
didn't
seem
to
work
very
well.
So
the
results
for
the
compound
which
is
22
3p
down
here,
gave
results.
That
indicated
that
that
certainly
didn't
solve
the
problem.
A
We
know
from
Laura's
spr
results
that
there
appears
to
be
a
good,
binding
interaction
between
that
molecule
and
mercy.
I
think
it
was
so
I
guess
we
were.
You
know,
assuming
that
the
problem
here
is
that
the
molecule
is
is
just
being
pumped
out.
So
the
addition
of
the
primary
doesn't
help
but
I
guess
we
do.
We
yet
have
any
evidence
of
it
inhibiting
the
enzyme
in
vitro
outside
the
cell
I.
Guess
we
don't
have
that
right.
So
we
have
to
make
the
assumption.
G
A
And
so
now,
yeah
un's
been
looking
at
some
other
art
bands
which
hean
who's
on
the
call
had
predicted
to
bind
and
which
we
put
aside
while
we're
trying
to
finish
off
the
amine
work
and
you
hang's
been
developing
the
chemistry
towards.
Certainly
the
comment
on
the
left
and
it's
got
plans
for
two
of
the
other
compounds
there.
So
just
to
get
you
in
the
loop
Yan
playing
around
with
some
of
this
chemistry.
A
A
F
H
Program
so
I
I,
obviously
having
a
crystal
structure
would
be
great,
but
in
in
this
case
you
know
there
are
crystal
structures
that
you
know
the
ssgc
ID
has
solved
for
the
AZ
series
now
I
think
where
we
have
three
three
several
different
systems,
and
so
on
so
I
I.
Think
in
terms
of
writing
up
a
a
proposal
for
them
to
do
some
Library
work,
I,
I
I
would
recommend
going
forward
with
that
I
mean
I.
Think
I
mean
I.
H
Look
I,
look
at
that
Equity
as
kind
of
what
your
lab
is
on
driving
Matt,
so
I
mean
it's
kind
of
in
your
in
your
I
feel
like
that.
That's
in
your
shop
to
to
to
do
but
I'm
willing
to
help
in
any
way
with
with
that,
but
I
I
would
encourage
you.
I
wouldn't
I'm,
not
sure
what
you're
necessarily
waiting
for
in
terms
of
a
structure.
H
I
think
you
know
the
sscc
idea
has
done
a
great
job
of
delivering
those
structures,
and
so
I
I
think
there's
some
rationale
to
to
make
a
library
proposal.
But
that's
again
anything
I
can
do
to
help.
I
can
do
that
and
I
think
there
are
some
data.
I
mean
I.
Think
there
is
some
data
coming
through
Adrian's
shop
right,
I
think
was
on
some
of
those
compounds.
It's
just
I
mean
we've.
H
H
We've
Adrian's
done
this
great
job
of
get
generating
the
data
we
need
so
anyway,
just
for
the
AZ
series,
I
think
there's,
there's
I
would
really
encourage
you
to
think
about
write
up
another
grant
for
some
place
or
if
you
want
to
get
some
compounds
made
I
mean
that's
a
resource
that
I
think
you
can
make
some
good
case
to
get
some
a
library
made
anyway.
That's
that's
my
thought.
Anything
I
can
do
to
help.
Let
me
know.
H
H
A
H
A
E
A
You
know
antibiotics,
but
with
some
of
the
data
we've
got
so
yeah.
No,
so
your
offers
really
appreciated
Joe.
Thank
you
and
I
I
think
you're
right.
You
know,
and
it's
also
one
of
those
things
where
it's
right
now,
it's
difficult
to
write
up
a
bigger
proposal
on
it,
I
think
because
it
is
basically
something
where
we
need
some
fairly
dedicated
chemistry
doing
to
to
push
us
over
the
line
for
a
bigger
thing,
yeah,
so
I
think
it's
a
good
scheme
for
it.
A
A
E
A
Great
all
right,
thanks,
I
mean,
obviously
you
know
as
a
discrete
piece
of
work.
We
had
a
bunch
of
people
suggest
compounds
which
we
then
made
the
the
cherry
on.
That
paper
would
be
if
we
got
some
kind
of
structural
information,
or
you
know,
validation,
that
one
of
the
compounds
is,
is
binding
and
is
inhibiting
yeah.
A
Hopefully,
the
the
compounds
we
bought
for
me
I
mean,
and
we
we
have
funds.
I
should
I
should
say
for
another
round
of
purchase.
If
we
want
to
do
that.
So
if
there
are
other
compounds
that
have
come
from
the
enemy
libraries
that
need
a
little
bit
of
SAR-
and
we
can,
you
know-
spend
a
couple
thousand
pounds
on
buying
a
bunch
of
compounds
that
would
enhance
that.
A
Then
we
have
a
little
bit
of
money
left
over
from
the
entrop
Grant
and
we've
got
a
no
cost
extension
until
the
end
of
March,
and
we
have
a
few
thousand
pounds
left
to
spend.
So
we
can
bolster
SAR
on
some
of
those
commercial
compounds
if
that's
of
Interest,
the
ones
that
we've
done
already
are
the
ones
that
we
know
about.