►
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/39
On the call: Professor Matthew Todd, Dr Dana Klug, Yuhang Wang, Dayang Usop, Giada Sabatino (UCL), Dr Chris Swain (Cambridge MedChem Consulting), Professor Chris Dowson, Becca Steventon, Laura Diaz Saez (University of Warwick), Lizbe Koekemoer, Gustavo Arrudabezerra (Diamond/Oxford), Bart Staker (SSGCID), Joe Eyermann (NEU)
A
All
right
so
we're
recording.
So
thanks
for
coming
along
everybody
to
this
merly
gays
meeting
on
the
9th
of
february,
and
we
have
a
a
small
agenda,
but
I'm
sure
a
lot
of
things
will
will
come
up
for
discussion.
A
A
One
of
the
main
names
of
the
project
at
the
moment,
which
a
few
of
us
have
been
talking
about
and
joe's
been
talking
about
forever
and
chris
has
been
talking
about
forever-
is
the
idea
that
we
could
maybe
get
two
different
merligase
enzymes
to
crystallize,
with
the
same
small
molecule
inhibitor
and
a
great
candidate,
for
that
was
the
the
az
compound,
which
was
crystallized
by
with
mercy
by
the
seattle
group
recently,
and
so
to
get
that
to
happen.
A
We
need
some
sample
of
the
aza
compound
and
joe
I'll.
Ask
you
in
a
minute
just
to
say
something
about
how
that's
going
in
terms
of
getting
samples
from
from
the
colleagues
that
ashwag
that
we
spoke
to
recently,
but
just
quickly
in
case
in
the
likely
event
we
need
to
make
it.
We've
been
thinking
about
doing
that
in
our
lab
and
and
eugene
has
been
trying
to
develop
a
decent
synthetic
plan
for
that
compound,
so
that
we
can
make
some
and
then
sort
of
pass
it
around
just
see.
A
If
I
can
share
my
screen,
it
refused
is
that
okay,
hopefully
you
can
see
this
now
and
hopefully
you
can
see
that
synthetic
scheme
there.
So
so
this
one.
A
This
is
a
slide
that
you
hang
made
and
just
goes
through
the
the
synthesis
which
we're
planning
on
doing,
which
is
some
lit,
some
of
the
original
lit
and
some
you
know,
kind
of
extrapolated
lit
and
there's
a
fairly
okay
apart
from
a
couple
of
early
steps
which
might
be
interesting,
fairly,
okay,
synthesis
towards
the
azid
compound,
which
is
that
guy,
hopefully
you
don't
see
my
zoom
controls
on
the
way
that
guy
there
and
we,
I
think,
are
very
easily
going
to
be
able
to
make
the
separate
enantiomers
of
that.
A
So
the
the
positive
and
then
the
less
active
enantiomer
of
that
compound.
So
eugene's
just
ordering
those
molecules-
and
it's
going
into
the
lab
this
week
to
get
started
on
on
trying
to
get
that
going,
hopefully
not
too
difficult.
A
A
This
alcohol
group
is
sticking
out
into
into
solvent,
essentially,
and
so
that
drove
the
design
by
dang
and-
and
you
hang
and
us
over
here
of
this
compound,
which
is
exactly
the
same
compound,
but
with
an
amine
there,
which
apparently
was
not
made
by
the
original
az
team
and
which
should
retain
the
same
kind
of
interactions
as
the
original
compound,
but
because
of
its
possession
of
a
primary
amine
should
do
better
against
gram
negatives.
A
To
do
that
requires
a
little
bit
more
trickiness
in
the
synthesis
of
getting
this
diamine
compound
and
we'll
certainly
be
doing
this
first
with
the
rasamate
just
to
make
sure
that
we
can
get
the
chemistry
working
before
thinking
about
single
enantiomers.
A
So
that's
the
sort
of
the
immediate
synthetic
plan
is
to
generate
enough
this
compound
that
we
can
share
it
around.
Ideally,
you
know
from
the
same
batch
so
that
people
can
have
access
to
this
and
see
how
we
go.
So
that
was
that,
that's
that's!
That's.
A
C
A
Yeah
and
then
the
other
thing
I
was
going
to
say,
is
just
an
update
on
the
atom
wire
situation.
So,
as
some
of
you
may
know,
atomwise
have
sent
us
92
samples
of
small
molecules
that
they
predicted
to
be
tight
binders
to
d.
A
I
think
it
was
they're
in
ucl
we
had
to
modify
the
contract
to
allow
us
to
ship
it
ship,
those
samples
to
diamond
and
warwick,
and
after
a
lot
of
really
not
very
much
and
a
change
of
personnel
in
the
legal
office
at
ucl,
which
I
wasn't
aware
of
until
a
few
days
ago,
we
we
look
like
we
might
be
getting
there.
A
A
Okay,
so
that's,
I
think,
pretty
much
all
we
we
haven't
done
anymore
synthesis
since
we
shipped
you
know
the
frag
elaborated
fragments
to
diamond
into
warwick
last
year,
so
we
haven't
done
anything
else
on
that.
So
I
think
that's
what
we're
up
to
have.
I
forgotten
anything
uclas.
D
I
was
just
messaging,
you
hang
because
I
think
lori
had
sent
us
one
of
those
starting
materials.
She
did.
E
D
A
A
Thanks
all
righty
joe
did,
you
want
to
say
anything
about
the
interactions
with
asia
because
they
were
really
productive,
and
I
just
I'm
not
quite
sure
where
we're
up
to
on
that.
F
So
yeah
I
mean
I
think
astrazeneca
has
been
extremely
helpful
and
I
would
say
almost
encouraging
I've
reached
out
a
couple
times,
so
so,
basically,
what
what
we've
done
is
so
astrozonica
just
for
those
who
may
not
know
they,
they
have
what's
called
open.
Innovation,
which
allows
is
a
program
that
where
they
will
share
some
of
their
compounds
with
with
outside
groups,
and
so
obviously
that
was
how
initially,
the
the
seattle
group
got
a
couple
compounds
that
they
did
crystallography
on
against
mercy
pseudo
pseudomonas
mercy.
F
So
we
were
obviously
interested
in
trying
to
get
that
same
the
same
compounds
to
possibly
you
know,
test
them
against.
You
know
another
isosign,
whether
it
be
e,
coli
or
or
also
against
mere
d.
F
So
so,
basically,
what
I
what
I've
done
was.
I
went
back
to
the
original
publication,
the
chemical
biology
publication,
that's
going
to
publish
from
your
c
and
pulled
out
five
compounds
because
one
of
the
things
we
the
the
challenge
is
with
this
is
that
so
astrazeneca,
basically
you
know
there's-
and
I
guess
chris
and
also
bart
stackart,
the
seattle
group
in
terms
of
getting
things
through
legal.
F
So
one
of
the
things
we
were
trying
to
do
was
order
to
ask
astrazeneca
to
share
a
small
set
of
compounds
and
hopefully
get
those
via
maybe
a
material
transfer
agreement.
The
bottom
line
is
there
are.
There
are
three
compounds
that
astrazeneca
has
available
out
of
that
series
of
your
c
inhibitors
that
they
have
available?
They
were
willing
to
share
so
really
where
we
are
right
now.
I
know
chris
nelson
has
already
submitted
his
proposal,
the
paperwork
and
so
on.
F
So
I'm
not
sure
where
that
stands
chris,
but
and
I'm
not
sure
where
the
seattle
group
is
at
this
point
I
mean
the
only
thing
I
can
say.
I
don't
know
if
that
comes
up
but
laurie
and
I
had
a
tc
with
bart
stacker
at
the
seattle
group,
along
with
peter
oroni,
who
was
actual
crystallographer
who's,
actually
stationed
at
ucb,
it's
a
pharmaceutical
company.
F
He
was
at
one
point
part
of
kind
of
the
the
seattle
structural
biology
group,
but
now
it's
at
ucb,
actually
here
in
cambridge
mass
and
he's
very,
he
was
very
enthusiastic.
So
so
I
think
I'm
not
sure
where
the
status
is
with
the
seattle
group
in
terms
of
ordering
the
compounds
for
the
on
their
side.
But
those
things
are
in
progress
and
this
it'll
be
really
it's
a
matter
of
astrozenic
is
willing
to
share
it.
F
It's
not
a
question
that
has
come
examples
for
three
of
the
compounds:
it's
a
matter
of
getting
it
down
through
the
legal
process.
So
it's
really
now
in
the
hands
of
the
gods,
pretty
much
in
terms
of
the
lawyers,
that's
where
we
are.
As
far
as
I
know,
I
don't
know
chris
if
you
had
any
feedback,
any
any
feedback
from
az
on
your
side
in
terms
of
after
you
submitted
the
proposal.
C
No,
no,
no,
I
haven't
jo
it
where
I'm
just
going
looking
through
my
junk
mail
and
all
the
other
lovely
places
outlook
puts
things
that
are
used
that
I
really
want
to
read
and
I
can't
find
I
can't
find
it
anywhere.
So
I've
not
heard
anything
from
them.
I
have
already
sent
one
poke
directly
to
the
az
folks
outside
of
the
open
innovations
group.
So
I'm
trying
to
remember
who
it
was.
I
I
think
it
was
kelly
gray
kelly
was
that
right,
I
can't
remember.
I
sent
it
to
you
but
yeah.
C
F
So
yeah
again
I
just
have
to
emphasize
that
the
folks
kelly
gray,
especially,
is,
I
guess,
she's
based
in
cambridge
uk
and
extremely
forthcoming
and
helpful.
So
so
I
think
we'll
get
them
eventually.
It's
just
gonna,
be
a
matter
of
you
know
the
timing
of
that.
So
we'll
see.
A
Is
is
it?
Is
it
essentially
with
with
them,
and
then,
if
the
compounds
are
are
around
that,
then
it's
a
it's
a
discussion
between
them
and
and
and
bart
who's
just
joined
I
bought
is.
Is
that
the
the
nature
of
the
the
next
discussion,
so
we're
kind
of
we
don't
need
to
do
anything
else
there
we're
kind
of
just
waiting
for
that
to
happen.
F
No
yeah,
I
think
I
assume
that
there
is,
after
chris
thousand
submitted
his
open
innovation
proposal,
that
there
is
some
process
that
goes
through
and
then
eventually
warwick
will
have
to
sign
a
document
right,
and
so
it's
it's
a
matter
when
astrazeneca
sends
the
the
legal
document
for
the
you
know
to
share
the
compounds
and
then
work
will
have
to
sign
off
on
it.
So
I
don't
know
where
you
are
bart
if
you've
actually
had
any
more
contact
with
kelly
kelly
gray
and
astrazeneca
around
submitting
an
open
innovation
proposal.
G
I
haven't,
I
have
not
submitted
that
proposal.
She
did
tell
me
that
I
think
that's
what
I
have
to
do
so.
F
Yeah,
so
if
you
need
help
with
that,
I'm
I'm
very
happy
to.
I
don't
know
if
I
can
do
that,
almost
quote
for
you
or
fill
it
out
and
then
save
it,
and
you
can
do
the
final
submission
anyway.
I
anything
I
can
do
to
help
it's
very
chris.
Did
it
maybe
chris
you
could
even
make
some
comment
about.
It's
pretty
straightforward.
I
think
right.
I
think
he
did
it
in
probably
10
minutes
or
something.
C
No,
I
didn't,
actually
I
didn't.
Actually,
oh,
it
took
quite
a
long
time.
C
C
Because
you
have,
you
have
to
add
a
proposal
as
well:
it's
got
a
clunky
thing
as
well,
where
you
can
add,
you
can
add
attachments,
you
have
to
add
attachments,
there's
no
way
of
retrieving
the
wrong
attachment,
so
I
had
a
kind
of
a
whole
snowstorm
of
attachments
that
went
on.
I
couldn't
take
them
off,
so
I
just
left
them
on
there.
So
perhaps
they're
still
having
to
read
all
of
them.
G
Well,
I
I
apologize
for
not
doing
that
I'll
try
to
get
on
that.
Unfortunately,
my
the
seattle
children's-
I
know
many
of
you
guys
have
worked
in
companies
and
stuff
with
difficult
legal
teams,
but
I
actually
haven't
ran
across
a
legal
team.
That's
hard
to
deal
with
in
my
own.
G
Except
for
maybe
a
sanofi,
I
think
was
pretty
bad,
but
this,
but
we
have
a
process
of
escalating
signatures
that
takes
about
six
weeks
to
to
do
almost
anything
so
because
every
person
has
two
weeks
to
do
something
and
then
anyways
the
so
I
should
get
that
started.
G
Have
you
have
you
all
right,
joe?
Are
you
in
peter
harany
speaking.
C
F
She
had
another,
I
think
previously
scheduled
international
conference
kind
of
thing.
I
think
so
lori
has
kind
of
been
taking
the
lead.
I
mean
we,
I
I
think.
Where
things
stand,
I
think
lori
contacted
you
recently,
so
just
for
the
team,
we've
actually
ordered
a
set
of
comp
compounds
from
enamine,
based
on
similar
hinge,
binding
chemotype
that
that
we
looking
to
the
seattle
group
to
potentially
try
and
crystallography
yeah.
We
have
received
those
compounds.
Yeah.
E
F
If
those
end
up
going
over
to
that
island
yeah,
they
have
to
go
to
bainbridge
yeah,
that's
there's
an
island,
that's
where
the
I
guess
this
the
crystallography
facility
is
yeah
and
and
then
I
guess
peter
somehow
has
support
over
there
to
get
things
into
trays
and
all
that
and
then
he
eventually
does
the
the
collection
gets
done
and
he
does
the
analysis
all
remotely.
Is
that
correct.
G
Right,
so
what
there
is
is
on
bainbridge
island.
It's
a
company
that
used
to
be
called
emerald
biostructures.
They
used
to.
I
worked
out
there
for
a
long
time
as
well,
but
they
are
the
the
crystallographers.
G
There
are
the
structural
biology
group
for
our
structural
genomics
project
and
they
are
also
the
structural
biology
group
now
for
ucb
pharma
because
they
were
purchased
by
ucb
pharma,
and
so
it's
all
sort
of
the
same
group
and
people
and
peter
ronnie,
who
was
the
one
who
actually
did
the
mercy
structures
at
the
time
he
worked
over
here
on
bainbridge
island,
but
he's
since
moved
to
boston,
so
he's
now
on
the
east
coast,
but
the
way
that
they
operate
is
sort
of
distributed
and
and
but
they've
done
it
for
a
year.
A
All
right,
that's
great!
Thank
you
guys.
I
I
was
gonna
move
on
to
ask,
for
you
know,
updates
from
from
diamond
or
warwick
that
come
up
and
then
just
to
make
sure
that
we
hear
from
the
the
new
people
who
joined
today,
maybe
haven't
been
to
the
previous
meetings.
It'd
be
great
to
hear
about
what
they're
planning
on
doing
chris
elizabeth
did.
You
want
to
say
anything
about
any
any
new
developments
along
the
the
murrah
ligers
and
particularly
evaluating
compounds,
and
so
on.
C
I'll
just
pass
my
pass
over
to
becca
to
see
what
she
has
to
say
because
I've
not
spoken
to
her
for
a
week.
So
I
I
I
I
don't
know
where
we
are
with
her.
H
We're
actually
pretty
close,
we've
done
all
of
lisby's
in
the
initial
essays
and
we're
now
testing
whether
they're,
actually
true
inhibitors
or
are
inhibiting
this
coupling
reaction
in
the
assays
and
we're
hoping
to
get
that
done
by
the
end
of
this
week
and
we're
also
hoping
to
get
dana's
compounds
all
into
the
solutions.
We
need
to
start
running
their
initial
testing
as
well.
H
H
They're
lisby's
ones,
which
were
binding
to
the
little
side
pocket,
not
any
of
the
ones
in
any
of
the
substrate
bindings
places.
These.
E
Quiet
is
a
htc
follow-up
on
one
of
the
pockets
that
we
saw
burning.
One
fragments
I
just
wanted
to
see
if
we
can
build
it
out,
so
we
got
binding,
but
we
showed
the
compounds
to
dynamite
last
week.
It's
really
really
greasy
and
we're
not
really
sure
it's
gonna.
We
were
actually
convinced
it
wasn't
going
in
it,
but
so
they
kind
of
got
us
a
little
bit
excited
with
this.
Now.
I
G
I
One
question:
so
those
fragments
you
you're
mentioning
those
are
x,
cam,
scream,
fragments,
yeah.
Okay,
thank
you.
A
All
right,
that's
great,
so
gustavo
and
and
and
laura
did
you
want
to
just
say
hi,
because
you've
not
been
launched
in
the
meetings
before
and
some
of
us
may
not
know
you.
J
Yeah,
hello,
I'm
laura
I'm
working
with
chris
dawson.
I
used
to
be
in
the
cc
in
oxford,
but
now
move
to
chris's
lab
and
I'm
gonna
be
doing
crystallography
on
the
newer
I
like
aces
project.
Hopefully
I'm
gonna
start
setting
up
the
first
mirror
e
crystal
place
this
week,
so
fingers.
I
Yeah
some
I
am
gustavo
with
zera.
I
was
a
senior
scientist
at
the
wyatt
group,
red
metabolic
and
rare
disease
at
segc
and
since
january
now
I
joined
frank's
group
as
a
team
leader
team
leader
for
protein
crystallography.
F
J
A
Okay,
great
any
other
comments
about
any
of
that
stuff
that
anyone
wants
to
raise.
A
I
mean
the
as
it
says
on
the
you
know:
the
github
issue:
we've
still
got
these
three
main
strands
and
wise,
fragments
and,
and
the
you
know,
modification
or
confirmation
of
the
azik
comp
band
and
any
of
its
simple
derivatives
in
a
in
a
target
based
way.
So
you
still
remain
the
three
options
and
I
think
the
you
know.
The
main
thing
remains
that
we
we
need
this.
You
know
some
confirmatory
evidence
of
a
new
hit,
or
ideally
you
know
two
enzymes
with
one
compound
bound,
so
that
remains
the
scientific
target.
A
Chris
wayne,
just
pinged
me
before
the
meeting
and
identified
an
interesting
funding
source
from
the
mrc
in
the
uk,
which
I
put
on
the
on
the
github
issue,
with
the
link
that's
shown
there,
which
has
a
it
opens
soon
and
and
the
the
window
ends
in
may,
and
it
looks
quite
interesting
and
relevant
unless
I've
misread
it.
So
thanks
for
pinging
that
chris
I
mean
may
is,
is
possible.
A
You
know.
If
we
got
the
data,
we
really
want
to
get
in
the
next
month
or
two.
Then
that's
that's
doable
in
terms
of
a
funding
opportunity
over
in
the
uk,
which
could
of
course
impact
everybody,
but
it
could
be
something
that's
good.
So
please
take
a
look
at
that
if
you
haven't
seen
it
because
I
think
it
looks
quite
quite
good
for
us
doesn't
help
raise
money,
for
you
know,
colleagues
and
friends
in
the
us,
but
it
would
allow
us
to
do
something
and
on
a
reasonable
time
scale.
F
Absolutely
yeah
yeah,
I
mean,
I
think
we
you
know,
I
guess
just
for
since
this
is
an
open
source
program
and
should
be
open.
You
know,
I
think
you
know
the
feeling
is
we
really
have
to
have
two
different
funding
grants.
I
guess
you
know
the
uk
has
to
have
their
own
and
I
think
the
us
has
to
have
their
own,
and
this
is
a
matter
of
trying
to
find
figure
out
the
best
way
which
chemical
equity
you
know
goes
into.
A
Yeah
yeah,
I
was
looking
there.
There
are
a
few
international
schemes,
one
is
the
human
frontier
science
program,
the
hfsp
scheme
and
it's
interesting.
The
the
eligibility
for
that
requirement
is
such
that
the
team,
the
team
members
who
are
applying,
which
usually
three
or
four
people
across
different
countries,
have
not
worked
together
previously,
and
I
think
this
call
constitutes
working
together.
I
think
unfortunately,
so
I
don't
think
we
can.
We
can
do
that
scheme
and
there
are
so
few
others
that
are
genuinely
international.
C
So
we've
put
in
our
warwick
welcome
partnership
funding
award
we've
had
the
first
reviewers
comments
back.
I
think
the
maximum
score
for
each
item
was
out
of
five
and
eighty
percent
of
the
score
items
were
five
out
of
five
right.
Two
two
of
them
were
four
out
of
five,
and
that
was
from
people
saying
what
about
the
ip.
So
I
have
to
write
again
just
to
just
define
them
as
an
open
source
project
and
write
to
our
tech
transfer.
C
C
Just
just
not
wanting
to
get
a
hoax
up
too
high
wow,
because
it's
it's
never
normally
normally
deemed
broad
enough.
The
the
different
groupings,
so
this
is
normally
kind
of
a
healthcare
interventions.
C
Science
thing
you
know
like
how
do
you
deliver
and
develop
a
new
vaccine
that
goes
all
the
way
through
from
you
know,
discovery
to
delivery
and
it
got
social
science
et
cetera,
et
cetera.
But
you
know
I'm
not
saying:
let's
not
have
a
go.
I
mean
we
can
have
a
little
explore
phone
at
the
program
manager
and
just
have
a
chat
to
them.
Yeah
good
idea.
C
Yes,
perhaps
the
open
source
angle
would
appeal
it's
a
big
piece
of
work
to
a
partnership
grant
so
yeah,
but
well
flagged.
Well,
then,
so.
F
C
It's
an
internal
part
of
money,
so
it's
a
better
than
usual
probability
of
funding,
so
funding
announcements
will
be
made
within
four
weeks.
I
I
get
the
rebuttal
back
this
week
and
it's
only
a
small
amount
of
money,
but
lots
of
levitt.
You
know
there
was
150
000
pounds
worth
of
leverage
and
and
so
yeah.
F
That
was
that's
a
critical
I
mean:
what's
your
funding
there
to
get
the
ht,
you
know
these
assays
up
in
high
throughput
format.
I
mean
that's
just
fantastic
and
that's
just
going
to
make
such
a
that's.
What
makes
the
absolute
difference
in
this
you
know
project
moving
forward.
So
that's
thank
you
for
putting
that
in.
It's
just
a
great
opportunity.
C
Yeah,
so
I
just
need
to
write
a
killer
reply
to
them.
Just
I
don't
know
what
the
competition
is.
I
know
there's
two
or
three
other
spin
out
companies
that
actually
are
traditional
ip
root
things,
so
I've
just
got
to
really
sell
this
as
making
warwick
look
good
for
trying
something
new.
A
A
Yeah:
okay,
great,
that's,
fantastic,
I'll,
try
and
write
up
some
action
items
and
to
do
things
on
on
the
github,
but
I
think
everyone's
doing
the
the
main
thing
they're
going
to
be
doing
to
advance
the
project,
which
is
awesome
yeah.
As
you
said
joe,
it's
really
great
to
see
some
comments
going
to
be
can
be
tested
in
work.
That's
really
fantastic!