►
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/44
On the call: Professor Matthew Todd, Dr Dana Klug, Yuhang Wang (UCL), Professor Chris Dowson, Laura Diaz Saez, Rebecca Steventon (University of Warwick), Lizbe Koekemoer, Gustavo Arruda Bezerra (Diamond/Oxford), Bart Staker (SSGCID), Dr Lori Ferrins, Dr Joe Eyermann (NEU), Peter Horanyi (UCB), Dr Chris Swain (Cambridge MedChem Consulting).
A
This
on,
I
hope,
that's
all
right
and
welcome
to
the
meeting
on
june,
the
8th.
Let
me
share
screen
so
that
we've
got
everything
in
front
of
us,
which
I
think
is
this
one,
and
so
there
were
a
bunch
of
actions
from
last
time.
If
we
just
want
to
quickly
run
through
those,
then
that
will
I'm
sure,
bring
up
everything
we
need
to
talk
about
anyway,
so
just
to
start
off
with
the
synthesis
of
the
azad
alcohol
compound.
A
B
B
B
Right,
it's
a
so
yeah,
so
the
next
step
was
to
attach
this
hydroxyl
aiming
to
the
other
glory,
and
hopefully
we
could
get
this
all
right
and
here's
a
plan.
I
tried
tried
another
route
for
for
the
previously
for
the
previous
five
five
member
core
which
the
desired
product
is
the
main
products
what
we
desired.
A
Yeah,
so
a
bit
of
a
surprise
that
this
material
at
the
beginning
was
giving
bad
yields
because
actually
most
of
it
is
not
what
it
says
it
is.
So
it
took
a
little
bit
of
time
to
figure
out
what
was
going
on,
but
this
has
now
been
made
and
so
that
one
more
coupling.
So
the
idea
is
then
that
we
can
ship
that
out
to
people-
and
you
know
it
should
be
active
based
on
what
we
know
and
if
we
can
generate
inhibition
data
for
a
couple
of
the
merli
gazers.
A
Likely
to
be
well
when
it's
made
it'll
be
completely
pure.
It's
just
to
start
a
I
had
stuff
in
here
that
we
had
to
get
rid
of,
so
three
quarters
of
the
sample
was
useless
and
then
once
it
was
pure,
it
works.
Okay,
this
this
yield
is
because
the
the
sample
wasn't
pure,
but
the
the
actual
material
is
fine.
Okay,.
A
A
A
A
D
A
A
A
F
F
G
F
F
A
F
G
H
G
C
H
B
A
I
mean
yeah,
but
what
I
wondered
is
whether
we
should
so
if
we
dilute
everything
up
in
dmso,
the
right
concentration,
you
know,
should
we
just
send
the
whole
thing
or
should
we
keep
back
a
milligram
for
something?
For
some
reason
I
don't
know,
I
don't
know
what
we
do
them
here,
but
is.
Is
there
any
sense
in
keeping
some
of
it
solid,
or
should
we
just
double
the
whole
thing,
because
that's
you
can
always
make
use
of
dmso
solutions.
F
D
G
D
G
G
F
H
G
G
No,
no
so
make
it
to
make
is
easy.
It
is
better
for
us
if
we
ship
to
laura,
because
laura
is
at
work
and
can
receive
the
parcel
where
I'm
not
a
diamond.
I
can't
receive
the
parcel,
so
we
will
know
if
it's
shipped
to
lauren
that
she's
got
it
and
it's
fine
and
then
she
can
just
bring
it
to
diamond
when
she
has
to
come
through
okay,
so
that
makes.
I
F
C
C
A
I
So
I
just
sent
some
off
to
her
yesterday
to
just
show
her
where
we're
at
it's
looking
quite
good.
We've
got
a
few
which
look
like
they
may
be,
hitting
obviously
we'll
have
to
check
that
they're
three
positives
once
we've
done
the
full
initial
screen,
but
it
is
looking
good
at
the
moment,
which
is
nice.
C
A
I
C
I
J
A
J
Well,
so
we
could
prioritize
them,
because
I
think
that
you
know
what
joe's
given
us
has
been.
You
know
very
kind
and
generous,
but
I
think
the
experimental
data
is
good
to
go
into
experiments.
I
think
that
I
would
prefer
that
at
all
possible
or
use
the
modeling
data,
together
with
the
experimental
data
to
sort
of
decide
on
what
to
prioritize.
A
H
D
A
H
Magnesium
but
the
crystals
didn't
defract
properly,
so
we
did
a
test
on
the
fraction
test
and
they
weren't
good.
So
we
need
to
go
back
and
put
it
fine
again.
I
want
to
hold
this
after
right
after
it.
So
now
I'm
gonna
get
again
new
protein
and
find
out
why
we
do
crystals
from
different
sources
like
elizabeth
had
some
crystals
on
and
mines,
and
they
were
all
really
bad,
so
that
needs
to
be
looked
at,
so
I'm
looking
into
it
now
now
that
I'm
back
finally,.
H
H
B
H
A
K
E
C
C
Illegal
yeah,
I
add
the
one
that
works,
so
I
submitted
for
access
to
the
compounds
as
well,
not
not
yours,
but
that
would
be
a
nightmare
if
yours
has
ended
up
in
ours,
it's
bad
enough
that
you're
dealing
with
their
own
yeah,
so
I
I've
just
been
pushing
them
on
the
on
on
the
atom
wise
compounds.
I
think
I'm
gonna
push
them
again
today
on
the
az,
so
yeah.
C
E
A
All
right
we
we
applied
for
the
antibiotics,
research,
uk
funding
on
the
28th,
so
we
ended
up
in
a
scramble.
At
the
end,
we
ended
up
putting
in
a
proposal
for
about
50k
to
drive
the
chemistry
to
get
compounds
made
with
the
understanding
of
those
would
then
go
to
to
work
and
and
oxford
stroke
diamond
who
were
the
co-applicants.
So
we
put
that
their
proposal
in
which
is
good
and
they've
received
it.
A
So
we're
waiting
to
hear
we
also
on
the
same
day
put
in
this
submission
to
the
european
lead
factory
call
they've
come
back
to
us
for
some
clarification
on
our
experience
today
with
the
assay
that
we
mentioned
in
the
proposal,
and
I
think
that's
with
christie
and
his
team
to
come
up
with
some
some
comments
about
how
the
assay
goes.
So
they
can
judge.
I
guess
how
easy
it
is
going
to
be
to
run
themselves.
Is
that
your
understanding
chris.
C
So
at
the
moment,
the
the
the
assays
in
the
what
the
assad
that
becky
uses
is
in
absorbance
mode
and
we
can't
run
a
high
throughput
assay
in
absorbance
mode,
because
you
need
to
get
everything
needs
to
crank
down
volume
wise.
So
it
needs
to
be
a
fluorescent
mode.
So
we
there's
a
coupled
system
that
we've
used
on
several
other
high
throughput
screens.
We
know
it
works
fine
and
we
know
it
will
work,
but
they
want
us
to
run
it
and
give
them
some
data.
C
So
I
think
what
I'll
give
them
is
a
holding
email
saying
you
know,
they're
not
going
to
be
deciding
until
when
is
it
going
to
be
their
decision
date
is
not
for
a
few
months
anyway.
So
as
long
as
I
can
just
keep
it
in
the
system,
that'll
give
us
a
few
months
to
actually
go
and
do
the
the
high
throughput
validation,
experiments
and
we'll
we'll
need
to
have
a
chat
locally
as
to
who's
actually
going
to
go
and
do
that.
But
right
we
will
get
that
sorted,
so
that's
not
a
hindrance.
Yeah.
A
Given
that
it's
antibiotics
is
a
pretty
good
assumption,
then
then
we're
free
to
do
what
we
want.
We
can
deposit
the
in
the
public
domain
and
we're
free
to
go
so
there.
If
we
were
all
happy
with
the
idea
of
a
short
delay,
which
I
think
was
a
couple
of
months
right
between
the
data
being
generated
and
being
released
publicly,
then
then,
then,
there's
no
conflict
between
the
two
between
elf
and
what
we're
trying
to
do.
A
J
So
we
didn't
see
any
density
for
the
initial
set
and
the
varices,
and
so
the
compounds
it
would
be
really
good
to
know.
You
know
if
us,
using
more
crystals
and
soaking
them
is
going
to
be
helpful,
we're
happy
to
soak
them
at
this.
That's
not
a
problem.
I
just
don't
know
you
know
if
we
could
have
the
any
kind
of
affinity
information.
J
I
think
that
would
be
super
useful,
at
least
on
the
concentrations
to
use-
and
you
know,
sort
of
give
us
a
little
bit
of
a
handle
on,
but
how
to
get
saturation
and
then
the
second
thing
is
about
the
mirror.
Ds
as
well
is
that
we
we
have
crystals
in
the
fraction,
but
we
can't
solve
the
structure
because
the
protein
is
crystallizing
in
a
peculiar
way.
J
So
in
the
interest
of
not
just
sort
of
going
hog
wild,
it
would
be
really
good
to
sort
of
get
a
little
bit
more
guidance
on
on
which
compounds
to
prior
to
focus
on,
because
the
four
that
with
the
joe
has
provided,
is
the
higher
priority
one
from
the
list.
I
think
that
that's,
if
you
could
get
down
to
two,
I
think
that
would
be
more
realistic
and
sort
of
understanding
whether
we're
going
to
be
able
to
get
something
on
a
short
order.
D
D
So-
and
I
definitely
hear
your
concern
about
you
know
not
just
burning
up-
you
know
valuable
protein
trying
to
defensive
trials.
So
I'm
not
sure
I
mean
one
things
we
we
we
could
do
would
be
to
in
theory.
I
guess
order
the
compounds
again
from
enemy
and
have
them
shipped
to
war.
Excuse
me
and
shipped
to
warwick
and
see
if
they
not
forgotten,
exactly
which,
because
they're
right
now
they're
running
your
80s,
really
weren't
tested
again
weren't
really
docked
against
mary.
I
think
these
were.
D
J
D
D
D
K
K
C
I
mean
we,
don't
we
don't?
We
can't
run,
you
know
all
of
the
protein
assays
all
the
time
so
becca's
got.
You
know
the
assay
running
for
these
compounds
so
she's.
You
know
100
occupied
on
that.
So
actually
we're
rate
limited
on
numbers
of
hands
for
the
assays,
so
we're
not
rate
limited
on
which
proteins
we
can
assay
it's
pairs
of
hands
to
assay
them.
C
J
Yeah,
that
makes
sense,
I
mean
really.
What
I'm
trying
to
probe
is
whether
or
not
there
is
any
room
for
someone
else
to
do
this.
So
what
we
can
do
is
we
can
do
like
a
biophysical
acid
like
a
dsf
and
see
if
we
can't
see
any
kind
of
thermal
stabilization
by
the
compound.
So
you
know
I
was
just
trying
to
sort
of
see
what
we
can
utilize
here
for
the
training
team.
J
J
J
Exactly
yeah
yeah,
so
that's
why
I
figured
it's
well,
we'll
try
we'll
come
back,
but
we're
gonna
see
what
we
can
do
with
the
crystals.
We
have
in
hand,
but
we're
not
gonna
set
up
any
more
trades
because
I
don't
want
to
blow
through
all
the
protein
without
the
right
set
of
data
first.
So
anyway,
that's
where
we
are
but
we'll
get
back
to
you
in
a
month
and,
like
I
said,
dsf
is
the
next
thing
for
the.
If
you
want
to
put
something
on
yes,
x9
that.
C
Would
be
really
helpful,
peter
just
to
go
through
with
laura
about
ordering
the
proteins
and
then
laura
and
I'll
have
a
chat
and
then
we'll
circulate
our
thoughts
on
what
to
order
with
everybody
else,
so
that
everyone's
in
the
loop
but
yeah
more
more
proteins
would
be
good
both
for
structural
stuff
and
for
assays.
So
we
can
just
as
we're
working
up
the
different
assays
we
just
plug
in
the
different
proteins
and
just
be
sure
they
behave
as
expected,
but
they
don't
always
becca.
Do
they.
J
K
Peter,
I'm
pretty
sure
you
can
guess
what
I
want
to
do
with
your
protein.
That's
with
your
bad
crystal
form,
so
we
should
probably
that
and
that
so
we
can
make
you
know
all
the
service
mutants
we
want
to
for
that
one,
and
that
would
be
something
we
could
do
over
on
our
side.
So
we
should
meet
to
to
plan
those.
I
think.
C
K
Right
yeah,
we
should
consider
doing
that.
That's
something
that
worsh
that
in
our
lab
will
be
shorthanded
to
do,
because
we
don't
have
the
way
that
we
operate
as
we
do
like
high
throughput
sets,
but
which
we
have
space
to
do
things
for,
but
we
don't
have
low
throughput
hands
to
do
side
projects
because
we're
because
those
are
all
doing
covet
stuff.
Basically,
so
that
would
take
more
time
for
us
to
do,
but
it
could
be
a
project
that
we
consider
doing.
K
C
And
and
and
then
also
multiple
mere
ease.
Obviously,
if
we're
going
for
a
de
inhibitor,
then
we'll
need
multiple
movies.
So
we'll
we'll
you
know,
as
joe
said,
we'll
close
the
loop,
let's
say
by
the
end
of
the
week
and
and
send
a
list
of
you
know,
requests
either
through
the
website
or
through
whatever
special
route.
We
need
for
a
low
throughput
option
request.
J
C
C
F
D
Yeah,
since
I
made
this
peter
that
the
two
compounds
you
solved
from
enthusiast-
a
z,
you
know,
against
mere
c-
I
mean
those
were
loading,
animal
or
I
mean
basically
one
nanomolar
compounds.
I
think
against
pseudomonas,
you
see.
So
you
know
what
are
the
dynamics
I
mean
I
know,
there's
some
issues
in
your
d,
for
example
with
with
dynamics
of
the
protein
so
yeah
these
compounds-
I'm
sure
you
know
my
guess
what
these
these
are
really
more.
D
Almost
like
x,
gun
fragments,
I
assume
they
were
probably
the
potency-
would
be
at
best
10
to
10
to
50.
Micromolar
would
probably
be
you
know
would
be.
You
know
optimistic,
maybe
for
some
of
those
fragments
leaving
my
guess
and
so
so
what
was
the
concentration?
I
assume
you.
You
were
screening
these
at
probably
at
a
hundred
ten
millimolar
or
in
terms
of.
J
J
J
You
know
how
do
we
get
to
the
saturation,
and
you
know
it's
the
only
way
that
we
can
see
it
in
a
crystal
structure.
Is
we
have
high
enough
occupancy
so
just
without
getting
too
far
into
the
weeds?
I
think
that
you
know
it
would
be
good
for
us
to
understand
which
ones
are
the
ones
that
are
the
most
potent.
So
we
can
start
with
those,
because
I
think
most
interesting
and
most
potent
are
not
always
aligned
and
yeah.
Just
getting
some
of
this
information,
I
think
it's
like.
J
J
D
D
Our
best
shot
on
goal
here
in
terms
of
ultimately
getting
you
know,
because
that
those
are
more
profiled.
You
know
and
get
the
biochemistry
on
those
and
and
then
hopefully
a
crystal
structure
and,
for
example,
your
d
or
your
e.
I
think
that's
the
shortest
path
to
proof
of
concept
for
dual
inhibition.
J
Yeah
sure
I
mean
crystallization
can
be
a
purification
method,
so
even
for
the
compound.
So
we
know
if
you
have
something
that
you
think
is
potent
that
has
the
potent
compounds
in
it
and
the
isomers
are
not
going
to
interfere
then
or
whatever
the
byproduct.
Is
it's
not
going
to
interfere
with
binding
that
you
know
we
could
always
try
that,
but
as
a
drug
development,
I
think
that
it's
always
good
to
have
a
second
series
or
a
multiple
series.
And
so,
if
you
know
that's
the
goal
with
the
different
data
sets,
I
think
it's
it's.
A
J
A
Okay,
thanks
for
that
and
there's
a
bunch
of
little
minor
things
here,
which
I
think
you
can
all
see
on
the
screen
about
our
interactions
with
alpha
fold,
david
baker,
lab
and
and
whether
or
not
you
know
we
could
soak
some
of
these
kinds
of
diamond,
which
I
guess
is
a
little
academic
given
what
we
were
just
talking
about
and
the
possibility
of
a
biochemical
screening
against
another
non-atp
site.
I
mean
I'm
gonna
leave
those
there,
because
I
don't
even
know
you
need
to
go
through
them.
C
Matt,
I
I
sent
you
some
options
for
the
alpha
fold.
Proteins.
Oh,
is
that
on
me
sorry
yeah,
I
I
I
sent
you
kind
of,
I
think
laura
chose
options
of
a
of
a
mere
c
d
and
e
with
a
crystal
structure
and
one
that
was
not
crystallized,
and
then
I
also
sent
you
you
know
a
tyrannosaurus
as
well
I'll
I'll
find
that
and
I'll
dig
it
out
and.
A
D
I'm
sorry
becca,
I
I
can't
seem
to
locate
your
file
that
you
said
you
have
you
uploaded.
Could
you
send
out
a
link?
There's
there's,
I
guess
various
different
pathways
in
github,
but
if
you
could
send
out
the
link
of
where
you
actually
uploaded
that
data
for
the
fragments
that
you
just
generated
percent
ambition
on
that
would
be
great.
We
appreciate
it.