►
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/102
On the call: Prof. Matthew Todd, 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
Chris
is
on
holidays.
Did
you
say
yeah
all
right,
great,
fine,
so
all
right,
so
the
the
today's
meeting,
I
guess,
is
what
I'd
like
to
do
is
start
out
with
the
the
data
that
you
guys
at
Warwick,
kindly
sent
over
on
the
testing
of
the
compounds
that
were
recently
shipped
by
yiway,
which
included
a
bunch
of
other
things.
There
too,
which
were
derivatives
of
some
of
the
atom-wise
and
competition
compounds,
and
things
like
that,
because
Adrian
you've
just
done
a
bunch
of
measurements
on
those
and
sent
that
through.
B
B
B
Okay,
all
right,
so
we
received
compounds
that
were
as
I
understand
it,
an
extension
principally
of
the
atomized
compounds
that
I
need
to
be
originally
screened,
and
these
compounds
largely
were
developmental
one
well
or
more
of
the
leads
that
she
extracted
from
that
screening
and
she
found
that
a
number
of
these
things
multi-targeted
and
what
I
was
saying,
was
as
I
understand.
It
The
Logical
extension
of
the
leads
that
you'd
want
to
chase
up.
B
B
B
B
D
D
B
So
the
net
result
was
that
you
could
I
can
see
to
my
rather
untrained
eye
repeating
motifs
coming
out
in
the
compounds,
which
kind
of
suggests
that
there
may
be
a
series
of
some
description
emerging
with
respect
to
merdi,
so
we
then
went
on
to
screen
e.
The
only
reason
this
box
is
here
is
that
I
gather
someone
might
actually
need
this
for
their
thesis,
so
these
are
the
actual
details
that
we
use
anyway,
with
a
with
the
screening
against
Murray.
B
Having
eliminated
all
the
compounds
that
we
would
worry
would
Target
the
coupling
system.
We
came
up
with
another
11
compounds,
most
of
which
actually
were
also
significantly
inhibitory
against
nerdy.
So
all
the
compounds
that
inhibited,
both
Murray
and
mo
Tito
and
greater
than
50,
are
highlighted
in
the
Box
on
the
right
hand,
side
in
that
maroon
color
and
the
ones
that
are
uncovered,
as
in
Black,
appear
to
singly
take
out
Murray.
B
And
finally,
this
table
basically
directly
compares
the
inhibition
data
we
have
for
mercury
and
muddy
where
we're
looking
for
those
compounds
which
have
at
least
50
percent
inhibition
potency
against
one
or
both
enzymes,
and
that's
the
data
that
we
send
you
and,
at
the
moment,
quite
literally,
we're
trialing,
verse
3.
With
this
compound
set.
We
should
have
data
by
I
hope,
the
end
of
tomorrow
to
be
sent
towards
the
end
of
the
week
and
that's
where
we
are.
A
All
right
great,
thank
you.
If
you
just
focusing
on
the
last
slide
there,
if
you
were
able
to
unshare
I,
could
try
to
I
could
try
to
do
something
useful,
which
would
be
to
I've
just
lost
the
tab.
Sorry
I
was
trying
to
share
the
compounds
that
we
had
yeah,
so
I'm
just
going
to
get
on
the
right
screen,
because
the
zoom
is
misbehaving.
E
A
A
As
you
said,
two
of
the
original
atomized
hits
so
things
either
made
or
purchased,
and
this
compound
four
that
came
from
the
competition
where
our
contributor
Finley
had
suggested
this
four
and
then
we
we
did
a
little
bit
of
SAR
by
catalog
around
that
and
it
comes
up
again
here
again
another
atomized
compound
and
that
compound
again
here
and
then
that's
kind
of
it.
There
are.
A
And
then
below
that,
so
you
can
see
it
on
the
on
the
GitHub
issue.
There
there
are
the
kind
of
the
others
which
which
there
are
structural
similarities
right.
So
you
know
there
are
some
e-way
compounds
that
don't
tend
to
work
quite
as
well.
There's
another
set
around
one
of
the
other
atomized
compounds
made
by
Eve
and
so
on
and.
E
A
A
As
if
all
of
these
compounds
are
hitting
there
they're,
certainly
not,
you
know
we
get
a
real
range
yeah.
These
are
some
of
the
scr
by
catalog
around
the
atomized
compounds
and
then
I
think
the
last
one
has
a
bunch
of
inactives,
essentially
so
yeah
there
were
a
couple
of
final
compounds
made
for
the
competition
which
didn't
do
you
terribly
well
and
then
another
another
bits
of
yet.
A
A
A
Yeah
awesome
but
I
mean
on
on
first
clients,
they're
they're,
they're,
it's
a
range
of
activities,
so
I
guess
with
some
of
these
compounds
they.
So
some
of
the
year's
compounds,
for
example,
the
solubility
was
always
pretty
bad,
so
I
was
worried
that
we
might
just
be
getting
aggregation
and
interference
with
the
assay
or
what
have
you,
but
it
doesn't
look
like
that's
the
case,
because.
A
A
Yeah
exactly
right,
yeah.
So
those
are
my
two
questions.
So
one
is
yeah
if
you
are
happy
to
get
the
ic50
data
for
for
the
best
compounds,
the
green
ones,
so
the
the
ones
that
are
hitting
both
you
say,
you're
also
doing
merci
in
the
same
kind
of
assay
and
then
yeah
the
possibility
of
crystallography
for
the
best.
Looking
compact.
C
A
C
A
A
C
F
A
Okay,
all
right
all
right,
wonderful,
so
yeah!
That's
that's
really
promising!
So
thank
you
very
much
for
doing
that
has
submitted
her
thesis
and
done
her
presentation
and
it
is
I
think
currently
on
our
way
back
to
you
or
in
China,
so
is
not
able
to
join
us
today,
oh
yeah,
when,
when
I,
when
I
hear
what
she's
got
it
so
great
I'll,
let
you
know,
but
a
very
nice
way
to
have
you
know,
data
on
the
compounds,
so
that
was
very,
very
useless.
She
got.
B
B
D
A
C
D
D
I,
don't
quite
understand,
I'm.
Sorry,
I
didn't
quite
understand
what
you're
saying
Laura
so
again,
I
just
think
these
were
not
they're.
Adam
wise
did
not
Adam
wise
did
not
as
far
as
I
recall
did
not
scream
in
the
ATP
site.
They
were
screening
at
the
like
x-chem
sites,
the
other
sites,
not
the
ATP
site.
We
we
I
thought
we.
You
know
we
went
through
this
whole
thing.
The
question
was,
you
know:
where
are
these
compounds
binding?
We
did
the
overlays
and.
D
The
atomized
compounds
were
kind
of
adjacent
to
the
ATP
site,
not
in
the
ATP
site,
as
I
recall,
anyways.
Just
the
point
being
is
that
these
compounds
are
probably
not,
and
that
was
back
to
why,
when
it
was
the
ATP
concentration.
So
these
compounds
you
know
have
to
if
they
were
binding,
an
ATP
site,
you've
got
basically
km
amount
of
ATP
found
right
or
in
the
assay.
D
These
compounds
were
probably
in
the
you
know,
several
hundreds
of
micro
molar
based
most
likely,
based
on
the
inhibition
at
500,
micromolar,
so
I'm
just
saying
these
I
think
these
are
probably
you
know
these
there's
nothing
wrong
with
that.
I'm
just
saying
you
know,
they're
they're,
binding
and
then
they're
inhibitory,
I.
Think.
The
key
thing
here
is
that
they're,
actually
inhibitory
right
and
when
you're
running
Adrian's
assay
is
somewhat
I
would
say
it's
a
functional
assay.
Then
right.
B
D
F
D
Correct
correct
I'm,
just
saying
it's
unlikely,
I
guess
my
point
being
is
that
there's
unlikely
these
are
ATP
exactly
ATP
competitive
compounds.
They
may
be
allosteric
functionally,
but
they're,
not
I,
don't
think
they're
ATP
competitive,
which
is
fine,
I
mean
that's
a
good
thing
and
they
seem
to
be
multi-targeting.
So
that's
all
good.
B
F
A
Would
yeah
definitely
the
case
that
they
were
designed
against
not
not
necessarily
the
ATP
site.
However,
when
atomized
saw
the
crystal
structures
that
we'd
gotten
and
that
there
was
this
conformational
change
that
had
happened,
and
they
were
surprised
in
the
sense
that
you
know
they.
They
hadn't
predicted
that
the
range
of
confirmation,
when
the
when
the
molecules
bound
so
I,
don't
think
we
ever
had
a
really
good
answer
as
to
whether
or
not
these
compounds
were
by
were
binding
in
the
ATP
site.
They
certainly
weren't
designed
to
be
that.
F
A
A
Even
if
the
compounds
don't
aren't
the
ones
we
ultimately
pursue.
It's
still
nice
to
try
and
get
something
out
from
that
separate
study
and
then
yeah
ic50
is
crystallography.
I.
Think
it's
everything.
So
that's
wonderful
thanks.
Thanks
boo
thanks
for
doing
that,
sending
the
data
and
then
talking
us
through
it.
A
A
Again,
once
he's
once
he's,
got
those
made
those
compounds
and
got
the
data
of
the
activity
against
the
enzyme,
so
the
entomology
data,
then
that's
a
complete
piece
of
work
too,
for
that
he
still
just
needs
that
ic50
of
his
amine
compound.
So
the
one
where
the
Acer
compound
has
been
transformed
from
alcohol
to
an
Amy
still
just
needs
that
crucial
bit
of
data.
If
that
is
in
the
pipeline
at
Warwick,.
F
So
because,
like
my
my
previous
aiming
compound,
were
a
bit
hard
to
preserve
like
if
you,
if
we,
if
I,
especially
it's
like
a
super
small
scale
like
10
milligrams,
each
time
for
the
small
scale
reaction,
then
like
it's
really
hard
to
make
a
HDL
salt
because
sorry
TFA
sold,
because
if
it's
got
too
concentrated
cut
my
ring
off.
If
I
make
like
HCL
thought
it's
in
dark
same
then
the
amount
of
compounds
were
not
quite
enough
to
like
get
a
to
get
precipitate
so
that
we
can
filter
out.
F
C
F
A
A
F
A
F
D
C
A
All
right,
wonderful
and
you
hang
sorry
sorry
Joe.
We
we
are
on
the
verge
of
sending
you
a
well
the
cc4
car
proposal
that
we
wrote
that
you
and
I
mostly
wrote.
I.
Think
he
sent
that
to
you
and
Yuan.
Did
you?
Were
you
open
to
get
some
feedback
from
Jonah
proposal
before
we
could
we
generate
a
new
version.
D
Right
so
so
I've
received
that
I've
looked
at
it.
There's
a
number
of
things
like
I
take
Johan
what
I
need
we
need
to
do
as
a
separate
call
to
discuss,
because
I
think
there's
some
things.
It's
easier.
Maybe
to
talk
about
I've
been
I've
been
away.
I
was
actually
on
vacation
for
like
10
days
so
anyway,.
E
D
A
A
All
right
good
to
talk
about.
Okay
last
thing:
Lori,
if
you're
still
on
the
call
there,
there
was
some
interest
from
Neu
from
from
Bob
Hansen
on
some
steel
projects.
If
that's
still
live,
then
I
guess
we
should
meet
separately
about
that
and
talk
about
about
what
that
might
mean,
because
some
of
these
you
know
recent
hits
that
we've
just
been
talking
about,
might
be
really
good
for
student
projects.
E
E
A
We
couldn't
accommodate
everyone
in
research
lab,
so
we
so
we
use
the
teaching
labs
and
the
popular
group
project
where
everyone
was
making
a
different
thing
and
it
went
really
well
so
their
main
compounds
and
they're
being
evaluated
right
now
and
and
some
of
the
student
feedback
has
been
that
they
they've
they
actually
enjoy
being
part
of
a
team
that
was
working
on
something
right
rather
than
on
the
research
lab.
So
it
it.
You
know,
contrary
to
it
being
just
a
crowdsourcing
project
they
actually
found.
It
was
quite
fun.
Oh.
A
A
A
It's
the
set
you
haven't
talked
much
about
that
before
all
right,
but
we
we
saw
some
preliminary
data
a
few
months
ago.
Yeah,
that's
right!
Right,
okay
and
you've
gathered
more
I
mean
yes,
it
would
be
wonderful
if
you
wanted
to
talk
about
that,
but
yeah,
maybe
next
month,
yeah
yeah,
right
yeah.
That
would
be
really
good.
A
C
I
need
Monies
to
find
some
tips
from
someone.
I
was
not
going
to
use
so
I
can
you
know
replace
whenever
I
got
some,
so
I've
got
some
previously.
You
know
we
need
to
be
it's
more
about
when
to
use
it
or
how
many
companies
it
gets
to
make
sure
you
can
get
the
maximum
of
it
because
I
don't
know
when
the
next
month
and
then
the
tips
are
going
to
be
around.
They
still
have
issues
with
production
of
chips.