►
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/87
On the call: Professor Matthew Todd, Dr Edwin Tse, Yuhang Wang, Dr Daniel Gedder (UCL), Dr Laura Diaz Saez (University of Warwick), Dr Joe Eyermann (Northeastern University), Dr Chris Swain (Cambridge MedChem Consulting), Dr Jan Abendroth (UCB Biosciences), Dr Bart Staker (SSGCID).
A
All
right,
thanks
for
coming
along
everyone,
it's
the
9th
of
august
2022-
and
this
is
the
open
source,
antibiotics
merligays
meeting,
and
we
have
a
few
people
here
who
are
not
on
vacation,
which
is
awesome.
I
did
generate
an
issue
just
now
for
this
meeting,
which
I
will
now
share
just
in
case
people
don't
have
it
and
then
we
can
start
receiving
updates
from
people
as
in
one
okay.
Here
we
go
so
that's
a
bit
small
okay!
A
Here
you
go
just
to
update
people,
so
I
went
about
a
week
ago
to
the
gordon
research
conference
on
new
antibacterials
in
italy,
and
it
was
a
really
good
meeting
very
interesting
and
lots
of
people
doing
some
really
fascinating
things,
and
there
was
some
policy
people
there
from
you,
know:
god
p
and
all
these
places.
So
it
was
a
good,
a
good.
A
lot
of
science,
which
was
really
great
and
and
people
were
certainly
interested
in
what
we
were
doing
our
model
and
what
we
were
doing.
A
A
B
B
A
Awesome:
okay,
because
I
was
talking
so
alastair
parks
presented
it.
I
think.
No,
it
wasn't.
Alistair
parks
presented.
Sorry
somebody
else,
peggy
podd,
something
yeah
the
lifehack
guy
presented.
Sorry,
I
can't
remember
his
name
just
know
and
was
very
happy
with
the
idea
of
all
this
stuff
going
towards
the
project,
which
was
awesome.
The
compounds
that
you're
talking
about
what
are
they
retesting
fragments
that
were
discovered.
C
B
A
B
A
B
D
No
just
to
clarify
the
life
arc
compounds
have
been
identified
through
spr,
yes,
correct,
right
and
so
now
you're
trying
to
do
enzymatically
to
see
if
they're
functional
and
so
on,
yeah.
Okay-
and
you
said,
when
it's
structures
I
mean
so
life
arc
hasn't
disclosed
the
structures.
There's
some
paperwork.
It
has
to
happen.
So
I
would,
I
heard
something.
D
A
B
C
B
B
A
A
That
came
up
was
the
so
the
the
accumulation
guys
are
the
people
who
are
measuring
compounds
accumulating
in
bacteria
and
who
are
trying
to
you
know,
formulate
rules
for
how
to
make
compounds
accumulate.
So
the
hergen
rothellab
and
other
labs
that
whether
they're
all
interested
in
in
trying
to
work
with
us
to
try
and
improve
you
know,
compounds
that
we're
designing.
A
We
can
work
with
them
to
try
and
help
do
some
compound
design,
but,
generally
speaking,
experimentally,
it
sounds
as
though
you
know
there
is
help
there.
If
we
wanted
to
have
accumulation,
characteristics
or
accumulation,
I
don't
know
data
kinetics,
measured
through
a
collaborative
endeavor.
It
sounds
like
there
are
people
there
who
can
help
us.
A
I
heard
that
there
were,
of
course,
there
are
groups
in
the
uk
that
do
this
too,
and
that
might
be
more
straightforward,
but
it'd
be
useful
to
have
a
sense
of
of
you
know
which
group
it
might
be
good
to
work
with.
If
say,
we
had,
you
know
50
compounds,
for
example
the
you
know
the
enemy
compounds
that
we've
been
talking
about,
or
you
hangs
compounds
that
he's
making
who
who
we
might
want
to
approach
to
measure
those.
C
D
So
I'm
I'm
quite
familiar
with
this
group.
It's
actually
worked
with
one
of
the
when
I
was
part
of
the
imi
several
years
ago,
when
I
was
at
astrazeneca,
so
I
worked
with
paula
ricciaroni
who's
at
in
italy
and
said
all
the
computational
side,
but
I
think
helena
out
in
oklahoma
would
probably
I
think
her
lab
must
be
doing
the
accumulation
stuff.
So
I
would
think
that
she
was,
I
think,
she's
the
pi
on
that
nih
grant
and
I
would
say,
she's,
probably
the
the
person
to
work
with.
A
D
Yeah
you
know,
so
I
think
it's
you
know,
that's
the
question
that
to
kind
of
try
to
figure
out,
you
know
what
the
team
wants
to
do
around
that,
because
you
don't
have
mice.
You
know
these.
First
of
all,
the
compounds
aren't
that
potent
at
this
point.
I
understand
you
know
this
is
the
whole.
You
know
like.
When
do
you
do
these
things
right?
Yes,
you
want
to
try
to
build
in
the
characteristics
I
mean.
I
know
you
know
that
article
that
was
published
again.
D
You
know
some
of
the
rules
so
so
anyway,
I
mean,
I
think,
that's
something
obviously
think
about
it
once
we,
if
you're
doing
chemistry,
because
the
next
steps
right-
I
guess
you
know
we
get
structures
and
then
you
get
a
new
grant
that
supports
more
chemistry,
resources
and
he's
starting
that
design
process.
So
but
that's
great
to
make
that
make
that
connection
matt,
yeah
yeah.
I
think
that's
that's,
and
that
may
be
something
you
actually.
D
D
C
D
C
D
C
A
Okey-Dokey
leave
that
with
me-
and
I
will
I
will
try
and
make
some
some
reach
outs
for
accumulation
stuff,
but
in
case
that
you
hangs
compound,
I
mean
it's.
You
know
it
would
be
great
to
get
those
measured
anyway.
So
the
difference
of
an
oh
to
an
h2
should
make
a
difference
to
accumulation.
If
we
can
have
that
measure,
that
would
be
awesome,
but
more
generally,
we
can
think
about
in
terms
of
compound
design
going
forward
all
right
I
wanted
to
get
so.
There
are
a
few
key
things
today
which
I've
highlighted
here.
A
C
C
C
B
So
basically
at
diamond,
I
got
crystals
from
ue
equilibrium,
the
near
the
in
the
presence
of
obviously
the
four
heats
from
the
enemy,
then
equal
and
your
d
with
adp
melted
completely,
so
I
couldn't
send
any
crystals.
I
also
sent
crystals
with
umi
without
magnesium
and
two
versions
versions
with
magnesium
and
the
compounds
are
this
one's
the
ones
that
we
are
calling
the
atheists
and
the
names
of
the
compounds
for
now
different
concentrations
of
compounds
and
as
well
different
time
soaking
times
right,
but
I
couldn't
see
any
ligands
there.
B
The
only
thing
I
could
see
of
something
happening
was
in
the
crystals
from
mirror
e
with
j06,
and
they
were
showing
a
more
close
confirmation
than
usual.
We
have
seen
this
before.
If
you
remember
yeah
and
the
rest
of
the
theme
is
not
new
crystals
yet,
but
I
have
done
different
rounds
of
crystallization
the
last
one
is
pretty
recent,
so
I'm
still
hopeful
that
something
will
come
out
from
it
from
that
and
now
I'm
running
a
lot
of
protein,
so
I
need
to
make
more
product
to
be
able
to
do
more.
B
Follow
ups
have
also
set
up
some
more
crystallization
plates
for
doing
soaking
on
different
compounds.
Whatever
we
get
whatever
we
have,
including
the
old
conditions
and
new
conditions
for
the
e
coli
d
with
umi,
because
there
was
a
secondary
condition
that
also
gave
me
a
structure,
and
I'm
also
looking
into
that
one
and
that
one,
I'm
still
waiting
for
crystals
to
grow.
They
took
a
bit
longer
to
grow
in
the
first
initial
screen.
So
it's
still
within
the
time
of
them
to
be
able
to
go
yeah.
B
D
B
D
C
B
B
D
D
B
So
there
was
less
precipitation
of
the
compound
right,
so
there
should
be
more
in
solution.
However,
if
that's
enough
to
get
the
crystal
sorry
the
compound
bound
into
the
crystal-
and
you
know
that
didn't
work
out
so
but
yeah
you
can
see
a
progression
on
compound
aggregation
and
concentration.
You
can
see
the
correlation
on
that
yeah,
so
I
think
it's
just
the
condition
is
not
ideal
for
this,
so
yeah,
I'm
hopeful.
The
new
condition
will
make
it
happen.
D
So
and
these
sorry
again
I'm
just
so
they
do
these
like
diffusion
experiments
or
something
where
you
have
like
the
solution
of
the
compound
and
basically
through,
like
diffusion,
you
understand
what
I'm
saying.
I
think
there's
these
methods
where
you
have
the
crystals
and
then
you
have
your
compound
in
like
a
reservoir
and
there's
like
a
diffusion
kind
of
experiment.
So
there
you
you,
basically
you
know
you're,
not
putting
the
compound
directly
in
it's
it's
more
like
a
diffusion
kind
of.
D
B
Yeah,
so
I
did
different
tests
on
the
concentration
and
the
crystallization
condition
that
they
were
all
you
know
showing
the
same
thing.
I
just
trying
to
think
if
that's
mimicking
the
dilution
so
as
soon
as
they
were
touching
the
condition
when
I
was
looking
at
the
microscope
as
soon
as
they
were
touching
the
condition
it
will
aggregate.
D
A
B
C
E
C
D
C
D
B
C
B
D
No,
I
think,
there's
some
compounds
reordered
to
have
a
news
new
stock
of
some
of
the
hits.
That's
what
I
think
both
laura
and
then
I
think
laurie.
Yes,
that
had
ordered
a
few
of
the
others
that
laura
hadn't
ordered,
but
I
think
they
were
all
around
just
the
actual
hits
nothing
no
near
neighbors
have
been
ordered.
As
far
as
I'm
aware,
okay,.
A
B
C
B
Yeah
it's
it
was
summer
students,
I
don't
know
if
they
will
be
continuing
yeah,
then
the
so
we
got
the
compounds
from
cato
from
ed.
Those
will
be
run
on
the
spr
and
essays
together
with
the
full
competition
essays
compounds.
Sorry
competitive
compounds,
so
we
will
merge
them
together
and
run
them
at
the
same
time,.
B
B
I
have
done
the
otherwise
compounds
on
the
spi
experiments
in
competition
with
amp
mcp,
so
I
will
update
that
in
the
in
github
gig
right.
Sorry,
I
can't
actually
so
I
will
update
that
as
soon
as
I
can,
as
well
as
the
results
on
the
pocket
from
atomwise
and
their
skimming
screens
in
summary,
is
the
same
pocket.
C
B
B
F
B
Yeah
and
on
the
queue
there
will
be
again
re-screening
enemy
against
all
the
new
ligases
in
case
we
are
missing
any
other
compound,
because
now
we
screen
only
against
one
protein
and
we
are
using
those
hips
and
see
if
they
have
potency
against
the
other
metagases
okay.
So
the
idea
is
also
re-screen
the
enemy
library
against
all
the
mela
gases.
So
that's
on
the
cure
as
well-
and
there
was
an
initial
compound
sent
to
us
a
few
years
ago
and
those
will
be
yes
well
included
on
the
screen.
C
A
Okay,
great
all
right
thanks!
Well
just
so
it's
a
good
segue,
because
I
think
that
I
guess
we
can
just
then
call
on
some
of
our
chemists,
so
you
hang
and
er
and
daniel
just
to
give
really
quick
updates
on
some
of
the
chemistry,
because
I
think
they're
all
they've
all
sent
or
are
sending
you
compounds.
G
Yes
sure,
so
what
for
the
compounds
I
made
and
I've
been
updated
below,
and
I
can
share
yeah
sorry,
so
I've
I've
managed
to
send
the
micro
ed
samples
because
they
require
way
less
than
the
microbiology
sample.
I
checked
last
week
with
laura
and
she
she
told
me
that
for
microbiology
for
these
five
samples
they
are
going
to
require
like
50
to
60
milligrams
each.
So
I
currently
have
four
four.
I
currently
have
four
four
four
of
them
having
having
this.
G
This
amount
to
be
shipped,
but
the
only
problem
is
that
aiming
is
the
amy
product
is
so
it's
really
hard
to
accumulate
to
this.
It's
like
each
time
it
got
like
five
milligrams
or
nine
milligrams,
but
like
if
you,
if
you,
if
you
scale
up
and
my
risk,
could
the
yield
so
my
still
ended
up
being
getting
like
10
minutes
less
than
10
milligrams.
So
I
I'm
trying
to
do
multiple,
I'm
trying
to
start
like
multiple
small
scale
reactions
and
try
to
accumulate,
but
definitely
need
more
time
to
like
purify.
A
A
D
Sorry
I
this
this
kind
of
blows
my
mind.
I
I
you
know
the
the
requirement
for
50
60
milligrams
for
doing
the
micro.
What
what's
going
on
there,
because
I
mean
sorry,
sorry,
I
I
don't
know
just
talk
about
my
you
know,
15
years
at
az
doing
you
know-
and
I
wasn't
in
the
microbiology
lab,
but
chemists
were
never
making
15
16
legs
to
to
do
microbiology.
So
I.
D
D
Two
to
five
minutes
should
be
enough
to
do
the
microbiology.
I
don't
understand
what
what
what's
the
requirement
here
for
such
a
large
amount
of
material
for
for
doing
some,
simple
micro
experiments
against
you
know
a
couple.
You
know
you.
You
basically
want
to
be
doing
pseudomonas
here
and
maybe
e
coli.
You
know
like
two
two
organisms
and
you
know
a
couple
different
concentrations,
and
I
I
just
kind
of
anyway
anyway.
Sorry,
but
I
just
yes.
B
C
B
A
B
H
C
G
C
D
B
A
A
C
H
So
I
think
laura
already
has
two
of
the
glue
enamine
compounds,
but
the
rest
of
them.
I
just
got
an
email
today
saying
that
they
were
ready,
except
for
that
top
right,
one
which
they
were
having
trouble
purifying,
so
we're
just
gonna
leave
that
one
out
in
terms
of
the
other
pink
ones.
So
I've
been
working
on
those
top
two
in
jan
jensen's
box.
I've
made
the
right
one.
I
just
need
to
do
one
more
purification.
H
The
left
one
is
a
bit
of
a
struggle.
I
think
it's
because
of
this
yeah
ring
in
the
middle.
It's
not
behaving
too
well,
but
I'm
trying
to
get
that
and
then
in
the
ucl
comp
side
box.
That's
we
have
to
make,
but
that
one
got
shipped
to
laura.
So
she
has
to
send
that
to
us.
Then
we
can
do
that
one
reaction
and
then,
in
the
bottom
box
the
middle
one.
H
A
F
Those
those
three
are
working.
I
have
the
current,
the
first
scoring
and
the
second
one
and
then
accurately
work
in
the
third
one
occurring.
My
biggest
problem
here
is
just
to
how
to
synthesize
the
diode.
I
repeat
the
reaction
a
couple
of
times
and
the
diode
is
not
working.
I
found
a
new
strategy.
I
will
try
this
week,
but
so
far
the
core
rings
is
ready.
I
just
need
to
fix
the
problems
with
the
dial
synthetic
artwork.
C
F
A
A
Okay,
all
right,
so
I
guess
we
we,
we
can
do
the
majority
of
these
things
soon.
So
I
guess
we
need
to
try
and
if
we're
going
to
polish,
these
off,
try
and
polish
them
off
in
that
kind
of
time
frame.
Because
then,
because
then,
if,
if
you
hangs
shipping
those
comments
to
laura
and
if
these
are
being
shipped,
then
it
would
make
sense
to
do
those
pretty
soon
all
at
the
same
time.
A
B
A
B
B
A
Okay
sounds
good
thanks,
guys
for
the
update
we've
got
like
50
minutes
left,
so
I
wanted
to
make
sure
that
our
structural
biology
friends
were
able
to
update
us
on
two.
I
think
new
structures-
and
I
just
want
to
go
back
to
where
we
were
here.
So
this
is
august
all
right,
so
yeah
last
time
yani
gave
us
an
update
on
some
of
the
stuff.
You
were
trying
on
wait.
I'm
not
sharing
screen
anymore
in
a
second
one
moment.
A
Last
time,
yeah
and
you
were
telling
us
about
some
work,
you
were
doing
on
these
two
structures
and
then
separately.
I
think
one
of
these
is
the
same
as
a
structure
which
came
through.
I
got
an
email
from
bart,
an
auto
email
from
bart
talking
about
this
structure,
and
then
we
previously
been
speaking
about
this
structure,
which
was
being
held
back
jan.
Do
you
want
to
summarize
this
much
more
clearly
than
I
possibly
could
yeah
so.
A
E
C
E
C
A
E
C
E
E
E
Once
I
tried
to
reproduce
this
crystallization
condition.
Most
of
the
crystals
had
eight
the
old
crystal
form,
with
eight
copies,
very
symmetric
unit.
Nothing
wrong
with.
That
is
just
a
lot
more
tedious
to
work
on
eight
molecules,
instead
of
just
only
one
but
I'm
in
the
process
of
refining
the
structure
hope
to
get
this
in
peer
review
today
or
tomorrow,
and
then
we
should
have
that
structure
shared
with
the
team
very
quickly.
A
E
C
C
E
Is
mirror
c
exactly
and
then
I
have
another
structure
at
lower,
similar
crystal
or
same
crystal
form
at
lower
lower
resolution
with
another
az
compound
and
also
co-crystallized
got
new
crystals
and
they
will
go
out
to
the
synchrotron
this
week
for
collection
on
friday.
So
hopefully
we
get
some
decent
data,
then
or
I
can
try
to
refine
the
lower
resolution
which
is
2.9
or
so
onstrom.
D
Those
just
a
quick,
quick
observation
just
for
those
kind
of
electrical
recognition
folks,
so
you
notice
in
this
that
there's
actually
a
carbon
to
the
to
the
asparagine.
You
know
the
conservative
sphere
gene
so
where
your
pointer
was.
It's
two
is
two
point:
nine
one
angstroms
from
the
carboxylase:
no,
no,
no!
No!
No!
No!
No
on
the
right
on
the
right.
D
Oh
this
one
here,
yeah
yeah!
So
so
you
see
this
in
kinases,
where
you
have
a
an
aromatic
ch
bond,
forming
kind
of
a
pseudo-hydrogen
bond
to
a
hydrogen
bond
acceptor
so
that
2.9
normally,
you
would
think
of
that
as
being
a
bad
van
der
waals
contact.
But
in
fact
this
is
one
of
the
things
we've
been
observing
when
people
are
starting
to
do
a
lot
of
kinase
kinase
hinge
binders,
where
you
get
aromatic
ch,
that's
forming
these
kind
of
hydrogen
bonds
to
hydrogen
bond
acceptor.
C
C
A
But
it's
interesting
because
you
know
we
previously
discussed
the
idea
of
a
purine
analog
right
where
that
would
be
converted
into
something
that's
favorable,
potentially,
even
though
geometry
is
a
bit
wrong
right,
but
that
would
ruin
the
favorable
contact.
That's
coming
out
northeast
there
right,
because
that
would
be
turned
into
a
ch
right.
C
A
A
E
C
E
D
A
A
C
E
A
D
B
A
Okay,
that's
great!
If
there's
nothing
else,
then
we
can
call
it
a
day.
Next
meeting
wait!
It's
right
there!
It
should
be
the
diary
ready
september,
13th
2
p.m.
Again,
please!
Let
me
know
if
there's
someone
who
is
not
being
invited
to
these
who
should
be
invited.
I
concerned
I
can
include
them
on
the
diary.
Invite
make
sure
that
please,
please
don't
hesitate
yan.
It
would
be
great
if
you
can
come,
but
we
understand
that
your
involvement
is
now
subject
to
other
pressures.