►
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/80
One-off meeting focussing on current status of crystallography in the project
On the call: Professor Matthew Todd, Yuhang Wang (UCL), Professor Chris Dowson, Laura Diaz Saez (University of Warwick), Lizbe Koekemoer (Diamond/Oxford), Dr Lori Ferrins, Dr Joe Eyermann (Northeastern University), Dr Jan Abendroth (UCB Biosciences), Dr Bart Staker (SSGCID).
A
Yeah,
so,
basically,
as
everyone
knows,
we
want
to
know
what,
at
what
stage
stages,
we
are
with
different
crystallization
efforts
with
the
different
organisms
and
proteins.
So
I
think,
if
john
can
start
updating
us
on
what
he
has
been
doing,
then
I
will
do
the
update
on
xcam
and
my
oh,
my
own
updates
and
and
then
we
can
discuss
the
future
things
yeah.
B
I
don't
know
what
you
can
see.
Can
you
see
the
presentation
view?
Okay,
awesome
so
yeah?
This
is
our
corporate
title
page
update
what
we
have
done
at
ssh
cid
and
I
want
to
start
off
right
away
with
a
big
list
and
it's
a
list
of
all
the
proteins
that
we
have
at
hand
and
ssg
series
in
our
freezers
for
mirror
c.
B
We
got
three
different
constructs
different
length
out
of
which
this
one,
the
bb5.
So
the
the
essence
you
see
the
ssgrd
nomenclature.
Is
you
start
with
the
organism
that
is
a
number
for
the
the
gene
or
the
protein
or
protein
family?
That's
the
family,
member
and
here
at
the
end,
the
b.
It's
it's
the
tac
version
and
the
number
here
at
the
very
end
designs,
whether
or
not
this
is
full
length
or
a
mutant
or
a
truncated
version.
B
I
have
listed
laura
I've
listed
that
at
the
end
as
well,
don't
have
to
write
that
down
here's
the
number
of
setups
we
have
done
for
each
of
these
targets
and
we
got
one
structure
for
the
acetylenobacter.
B
Muoci
is
the
the
amount
of
protein
that
we
have
left
in
our
freezer
to
see
on
bain
ridge,
we
got
a
few
more
for
the
pseudomonas
protein.
Mostly,
these
are
full
lengths.
When
I
was
setting
up
the
slides
yesterday,
I
couldn't
quite
figure
out
what
all
these
k1
k11
k12
k13
variants
are.
There
was
no
information
of
that
in
our
database.
B
B
They're
almost
exactly
the
same,
there's
one
point
mutant
halfway
through
yeah,
but
I
don't
know
why
there
are
four
so
there's
only
one
lysine
to
arginine
mutation
along
the
full-length
sequence.
C
A
look
yeah,
it
would
usually
be
like
a
surface
mutant
or
something.
But
if
you
say,
there's
no
changes,
then
that's
weird.
B
It
is
strange
and
we
have
a
decent
amount
of
protein-
that's
that
is
weird
too.
So
we
will
follow
up
on
that
and
we
include
that
at
the
end
of
the
slides,
what
these
actually
are
and
then
again
number
of
trays
that
we
set
up.
We
got
three
structures
for
this
truncated
version,
so
the
one
that
started
16
and
has
a
160
ish
residues,
truncated
at
the
end.
B
For
murder,
we
have
way
fewer
constructs,
but
we
also
get
more
structures.
We
got
for
the
cetinabacter
one
we
got
in
april.
We
got
an
adp
bond
structure
and
the
same
for
the
pseudomonas
protein,
but
we
hardly
have
any
protein
left.
B
A
B
Good
news
is,
we
got
crystals
very
quickly
and
they
will
be
looked
at
tomorrow
at
aps,
so
hopefully
tomorrow
I
will
be.
I
will
know
more
of.
D
That's!
That's!
That's
great
news.
Sorry!
This
joe,
is
just
something
I
think
you
know
this
inclusion.
Excuse
me
of
uma.
I
think,
excuse
me
sorry,
hopefully,
and
it's
you
know
or
ordering
things
a
little
bit
more
yeah
so
because
I
think
laura
will
show
that
as
well,
so
that
that's
great
that's
great
news.
B
Yeah
yeah,
it
was
very
exciting
to
see
how
quickly
those
crystals
grew
here,
quick
summary
of
the
structures
that
we
have
so
for
the
city
of
bacteria.
We
got
one
structure
a
for
protein
for
pseudomonas
aerogenosa.
We
got
three
structures.
They
all
superimpose
extremely
well
turns
out
they're
all
stoked,
so
the
general
trend
for
mirror
c
is
we
got
plenty
of
protein,
it's
pretty
difficult
to
crystallize
and
well,
since
these
are
soaked
it's
april
and
ligand-bound
at
least
for
the
pseudomonas
museum.
B
They
have
the
same
crystal
form
for
mere
d.
We
got
these
four
structures,
three
of
them
at
very
nice
resolution
between
1.5
and
1.95,
and
then
we
got
this
slightly
painful
structure.
I
remember
refining
that
that
was
quite
flexible
and
what
we
see
in
general
here
is
a
superposition
of
april
and
adp
bound
near
d
from
acetynabacter.
B
There
is
a
distinct
conformational
change
sort
of
this
pacman
move.
It
opens
and
closes
with
an
armistice
of
more
than
three
angstrom
and
the
same
we
observe
for
the
pseudomonas
one,
and
the
here
is
a
superposition
of
both
apo
and
both
adp
bond
structures
and
they
superimposed
a
bit
better.
But
we
are
still
in
the
range
of
1.5
1.8
angstrom
rmsd
in
general.
B
We
got
limited
neurons
of
protein
is
that
we
got
significant
changes
upon
adp
binding
and
they
tend
to
crystallize
pretty
straightforward
both
for
april
adp
uma
with
for
the
acetinobacter
protein
and
at
least
for
adp
and
uma
bound
for
the
pseudomonas
protein.
D
So
sorry,
so
I'm
just
sorry
yeah
good
good
question.
So
do
you
have
any
of
the
uma
left
to
try
with
acenetobacter
near
d.
D
Okay,
the
reason
I
mean,
I
know
sorry,
just
kind
of
as
a
general
comment
here.
Obviously,
we've
been
thinking
a
lot
about
pseudomonas,
but
you
know
there
is
a.
There
still
remains
a
big
need
for
asnetobacter
I
mean,
for
example,
in
tasis
I
mean
that's
one
of
the
pathogens
they're
going
after
in
their
clinical
trials.
D
So
just
as
overall
for
the
organ
for
the
effort
that
we're
doing
you
know
thinking
about
acetobacter
may
be,
you
know
something
that
really
should
be
thinking
about
in
terms
of
a
clinical
need,
and
if
you
get
crystals
you
know
for
us
need
a
backer
with
uma.
That
would
be.
That
would
be
great,
and
I
don't
know
if
that's
something
we
can
talk
about
later
in
terms
of
how
to
follow
that
up.
You
know,
overall,
for
the
project.
B
Okay
and
then,
lastly,
we
did
some
nano
dsf
experiments.
These
are
the
two
that
I
could
find.
We
first
got.
We
got
a
first
batch.
These
are
the
numbers
I
could
get
out
of
our
internal
report.
There
really
was
no
change
for
any
of
these
proteins
and
then
we
got
three
more
compounds
a
little
bit
later
and
we
could
see
decent
shifts
for
both
acetobacter
and
pseudomonas
miura
c,
but
nothing
for
any
of
the
murders.
B
I
had
set
up
limited
amount
of
trace
for
these
two
constructs.
With
these
three
compounds.
I
realized
I
could
do
more
and
if
there
is
the
wish
I
can
definitely
set
up
since
I
have
plenty
of
protein,
I
can
just
request
a
bunch
more
trays
just
to
make
sure.
Hopefully
we
can.
We
can
get
something
out
of
that.
B
As
I
said,
c
has
been
quite
difficult
to
crystallize
in
our
hand,
but
maybe
by
just
throwing
a
lot
more
conditions
at
it
and
using
the
optimization
conditions
that
yielded
the
april.
Crystals
might
hope.
D
Good,
so
so
I
would,
I
would
be
extremely
interested
again
just
following
up
on
the
s
needobacter
portion,
you
know,
with
the
az
compounds,
getting
a
acenetobacteria
c
structure
with
one
or
more
of
the
az
compounds.
That
would
be
great
right
because
I
don't
think
you
know
that
again,
that's
not!
We
don't
have
any
biochemistry
in
that
space.
I.
D
We
have
any
capabilities
for
that,
but
in
terms
of
publication
and
thinking
about
again
just
following
up
in
terms
of
going
after
acenetobacter
that
that
that
would
be
great,
you
said
you
okay,
but
you're
not
again
for
the
az
compounds.
I
guess
we
haven't
seen
any
activity
with
your
ds.
As
I
recall,
both
in
laura's.
C
D
And
your
lab
so,
but
in
terms
of
your
c,
I
think
that
would
be
ass
need
a
backer
structure
with
an
az
compound
would
be
that's
clearly
like
publishable
and
would
be
of
interest.
Yeah.
B
I
can,
since
I
see
there
is
distinct
interest.
I
can
request
criticization
setups
right
away
today.
D
B
Yeah
good
good,
okay-
and
this
I
need
to
finish
up
on
this-
is
sort
of
a
list
of
our
tags.
The
naming
scheme,
if
it's
called
b1,
it's
full
length
b,
yeah
yeah.
C
B
B
C
B
Do
you
know
if
what
kind
of
tags
they
have?
I
couldn't
just
steer
that
out
of
the
way.
C
C
D
That's
great,
that's
great
john
just
you
know,
at
least
for
me
what
what
you
guys
have
been
contributing
all
along
the
way
is,
is
really
really
appreciated.
A
Yeah
all
right,
so
I'm
just
going
to
give
an
update
on
everything
we
have
been
doing
for
eskim,
laser
pointer,
so
starting
with
e-coli.
This
was
one
of
the
initial
efforts
that
we
were
doing.
It
was
started
by
lisbon,
the
hcc
so
there's
a
lot
of
libraries
that
have
been
tested
for
this
particular
system.
The
crystallization
condition
has
isopropanol,
which
makes
the
mounting
of
the
crystals
quite
difficult
and
lengthy.
A
So
we
have
always
trying
to
get
those
conditions
better
to
get
less
isopropanol
or
zero
isopropanol
into
the
crystallization
conditions,
but
everything
we
have
tried
to
get
april.
Conditions
for
mu
e
have
hasn't
worked.
So
I've
tried
a
lot
of
different,
so
I've
tried
11
different
commercial
screens
with
three
different
product
concentrations:
two
different
temperatures.
A
A
A
D
A
Yeah,
the
library
summary
of
everything
that
we
haven't
tested,
so
the
s-cam
fragments
could
mean
the
enemy
library.
Then
another
library,
from
s
cam,
that
is
the
fragile
frag
lights.
A
Also
tobias
and
lisbei
bought
some
follow-up
compounds
for
the
new
pockets
in
ligand's
heat
star
we
obtained
in
the
x-cam
screen,
and
then
I
also
run
the
wise,
the
china
extras
and
the
dual
inhibitors,
but
we
got
really
poor
heat
rates
right
and
a
lot
of
them
were
binding
into
this
new
pocket
that
we
saw-
and
this
is
the
examples
of
the
new
pocket-
and
we
can
only
see
this
pocket
when
these
components
are
present.
If
not,
that
pokemon
doesn't
exist.
The
sixth.
D
A
A
So
that's
for
new
e!
Oh
I
in
the
case
of
the
dual
inhibitors,
I
couldn't
see
any
compounds
bound,
but
I
could
see
some
movement
of
the
structure
looking
into
a
more
compressed
conformation.
A
A
Then
in
the
case
of
e-coli,
these
are
the
conditions
for
the
best
diffracting
crystals,
mere
d
likes
equal
and
your
deluxe
to
crystallize,
with
ammonium
sulfate
and
with
low
concentration
of
protein,
and
he
stacked.
If
you
remove
the
his
tag,
near
d
does
not
crystallize.
In
an
april
conformation
now
I've
tried
to
do
or
find
other
apo
conditions
as
well,
because
when
I
run
compound
soaking
on
these
new
e
crystals,
there
was
this
pocket
formed
between
different
subunits
in
in
the
asian
in
in
the
packing.
A
So
this
pocket
is
an
artifact
from
the
crystallization
condition.
This
can
be
a
problem
because
it's
a
really
nice
pocket,
it's
quite
big.
So
it
has
here
one
part,
and
it
continues
on
at
the
other
side
of
the
protein,
and
it
combine
a
lot
of
different
things.
So
it's
not
ideal
for
running
this
scam
with
small
molecules
of
fragments.
So
I
was
trying
to
look
for
new
conditions
with
able
new
d
and
that
only
gave
us
more
able
crystals
in
the
same
packing
confirmations
with
this
one.
A
I
did
work
and
also
lisbon
catos
and
did
some
other
crystallization
as
well,
and
everything
was
in
the
same
packing
so
yeah,
basically
from
disable
efforts,
we
see
a
really
low
hit
rate.
The
protein
flexibility
seems
to
be
a
real
issue
for
both
e
e
coli
and
mu
e
and
mu
d
and
new
d
crystals
is
in
the
same
packing
all
the
time,
so
we
can't
really
get
that
forward
and
in
terms
of
of
the
atp
pockets,
because
this
is
an
open
confirmation.
The
atp
pocket
is
not
fully
formed.
A
So
if
we
want
to
target
that
pocket,
it
seems
clear
that
we
need
to
move
into
more
close
conformation
to
do
this.
So
I've
did
a
few
crystallization
conditions
in
the
presence
of
different
ligands
for
mu
e
adp,
atp
ampc
beam
and
the
three
peptide
some
phosphate,
as
well
just
in
case
and
dual
inhibitors,
and
none
of
these
showed
any
good
crystals.
A
They
were
all
apocryphas
in
the
same
april
conditions
that
I
was
getting
before
and
I
got
some
crystals
with
the
dual
inhibitors
in
a
different
condition,
but
those
had
really
poor
resolution
like
around
eight
amps
resolution,
so
I
couldn't
do
much
with
them,
but
in
the
case
of
near
the
nearly
likes
to
crystallize
on
many
different
things
like
gen
has
reported
as
well.
A
D
So
there's
a
so:
there
is
a
there's,
a
mtv
like
tuberculosis,
muri
crystal
structure
and
protein
data
bank,
which
has,
I
think
it
has
adp
and
one
of
the
uma
or
used
substrates
bound
yeah.
So
I'm
not
sure
what
you
can
learn
from
that
particular.
You
know
mtb
structure
in
terms
of
what
conditions
they
used
and
so
on
anyway,
just
just.
A
Yeah
I
was
trying,
so
the
condition
here
for
the
three
peptide
is
the
same
condition:
a
concentrations
and
all
that
that
is
published
for
the
other
e
coli
new
e3
peptide.
A
A
Structures,
neody
adp
is
1.7
astronauts,
quite
good,
a
and
pcp
to
answers.
Also
good.
You
can
see
all
the
densities
are
really
nice.
Everything
is
very
clear.
You
can
see
the
adp
and
the
magnesium
and
the
a
and
pcp
and
the
two
magnesium
bound
is.
You
know
everything
as
expected
and
in
the
case
of
them
you
collide
umi.
We
have
two
copies
in
the
asymmetric
unit
and
there
are
some
differences
in
the
umi
of
the
alarming
position.
A
A
A
A
A
So
I
will
refine
them
and
put
them
in
the
pdb
next,
so
this
is
a
comparison
between
in
the
atp
sites,
so
the
first
figure
is
mu
d,
with
adp
and
mu
d
apo,
the
april
structures
that
we
we
are
obtaining
from.
You
know,
x,
game
and
all
that
and
all
the
efforts
we
can
see.
A
Obviously,
here
the
shift,
there
is
a
big
shift
that
does
not
completely
the
the
packing
of
the
acti
of
the
binding
site
of
the
atp
pockets
and
the
second
one
is
adp
with
murdi
and
the
umi
structure,
and
you
can
see
they
are
pretty
much
very
similar.
There
are
some
differences
in
the
loop
here,
but
they
are
pretty
similar
and
I'm
quite
happy
to
follow
this
up
and
do
soaking
on
these
structures
in
terms
of
following
up
the
adp,
binding
structures
or
adpcp.
A
So
I
would
you
know,
I'm
starting
plates
on
those
follow-up
plates.
So
I
think
now
the
plan
is
clearer.
I
think
we
should
follow
up
the
close
confirmations
for
that.
We
got
between
the
ssccid
and
here
and
warwick,
and
then
and
and
then
once
we
get
those
structures
do
skim
soak
in
anything.
A
We
want
with
all
the
history
we've
gotten
so,
including
the
recent
inhibitors
from
then
I
mean
screening
in
the
essays,
as
well
as
the
initial
dual
inhibitors
that
we
got
and
other
skins
inhibitors
that
we
might
get
in
the
future
now.
I
also
think
we
need
to
do
some
crystallization
on
the
nice
inhibitors
that
we
are
getting
at
the
moment
from
the
end
amine.
A
We
need
to
try
that,
even
though
there
are
still
micro,
molar
binders,
but
I
think
we
should
go
ahead
and
try
some
stylization
just
to
cover
all
the
bases
and
again
try
soaking
of
compounds
with
well
april's
already
grown.
A
So
I'm
gonna
try
the
the
inhibitors
that
we
got
from
then
I
mean
try
to
soak
them
into
the
ap
crystals
and
and
then
once
I
get
the
crystals
for
the
other
things
all
the
same,
and
we
should
do
follow
up
with
what
jan
has
been
doing
in
the
ssgcid,
because
I
think
it's
quite
nice.
If
we
can
get
those
structures
with
other
organisms,
would
it
would
be
quite
nice
to
do
that
as
well
yeah
and
then
I
haven't
started
the
music
yet,
but
that's
something
that
is
on
my
plans.
A
A
A
D
So
I
guess
I
have
two.
I
guess
two
things
the
first
one
actually
is,
I
think
you
and
yon
and
ssgcid
should
be
thinking
about
a
publication
on
you
know.
So
I
know
I
know
bart
and
ssgcid
are
always
keen
on
you
know
they
generate
all
these
structures
and
then
no
one
picks
them
up
and
publishes
that
you
know
it
gets
deposited
into
protein
data
bank,
but
doesn't
get
published
in
the
peer-reviewed
journal,
and
I
think
now,
you've
collected
quite
a
few
new,
mere
like
ace
structures.
D
So
I
think
that
that
would
be
something
you
guys.
You
know
especially
like
well,
I'm
thinking
laura,
especially
in
terms
of
as
for
your
development,
professional
development
having
things
coming
out
of
your
your
work.
So
I
think
that
would
be
something
that
you
guys,
you
know,
can
work
together
on
that'd.
Be
my
if
there's
anything
I
do
to
help,
but
I
mean,
I
think,
that's
something
you
guys
should
be
thinking
about
more
in
the
near
term.
Actually,
and
that's
also
great,
for
you
know
future
grant
applications.
D
You
know,
as
we
try
to
follow
up
with
you
know
some
proposals
to
get
further
grant
funding
the
other.
The
other.
Is
this
actually
a
question.
This
is
actually
just
a
question
so
in
terms
of
the
x-cam,
so
doing
all
this
doing
the
additional
work
to
get
x-chem
ready
systems.
D
What
does
that
actually
mean?
In
terms
of
I
mean
from
from
from
my
side?
I
guess
just
put
it
from
my
side.
You
know
we're
you
know.
Normally
in
a
at
this
point,
we
would
have
you
have
some
hits.
It
would
be
great
to
try
to
get
you
know
either
soaking
or
co-crystallizations
with
the
systems
you
have
in
place.
You
know
how
much
more
optimization,
so
I'm
normally
thinking.
D
Of
crystals,
as
opposed
to
you
know,
if
you
could
get
you
know
a
handful
of
crystals
to
try
with
some
of
the
hits
that
are
having
hand.
That
was
just
in
terms
of
timing
and
well.
A
That
that's
going
to
happen
so
as
soon
as
I
get
enough
crystal
to
test
the
current
hits
from
them
and
amino
screening,
I'm
going
to
try
to
soak
into
those
crystals.
Oh
okay,.
D
A
Yeah,
that's
for
sure,
but
if
we
want
to
run
an
sk
screen,
we
need
to
have
a
highly
reproducible,
crystallization
condition,
and
you
need
to
optimize
that
sometimes
it's
really
straightforward.
Sometimes
it's
the
same
condition
you
found
the
crystal
in
and
it
gives
you
90
percent
of
your
crystal
plate
with
crystals
and
some
other
times.
A
It
takes
more
time
than
that
things
like
how
the
accurate
is
the
robot
that
you're
using
or
the
temperature
in
the
room
or
the
vibration,
the
all
those
things
can
make
a
difference.
You
know
it's
not
only
the
compounds
on
the
conditions
that
are
inside
yeah,
so
we
need
to
get
to
a
decent
resolution
reproducibility
in
terms
of
crystal
forming
and
crystal
resolution
as
well,
because
you
know
you
can
have
100
crystals,
but
if
only
two
of
them
diffract
at
two
angstroms
and
the
rest
of
them
are
three
angstroms.
A
D
Right,
I,
I
guess
it's
just
you
know
from
my
side
again
sorry,
I'm
just
kind
of
repeating
myself
here,
but
from
a
project
drug
discovery.
Moving
forward
with
you
know
trying
to
do
chemistry
with
some
of
the
hits.
You
know
how
how
are
they
binding
and
so
on?
I
mean
at
this
point
we're
not
per
se
looking
to
from
my
side
we're
not
looking
to
screen.
You
know
a
thousand
compound
library.
At
this
point
I
mean
we
have
some
hits
that
we're
trying
to
understand
how
they
bind,
and
so
I
I
know
laura.
D
A
A
D
D
I
guess
the
only
thing
at
this
point:
we
don't
actually
have
e
coli
biochemical
data,
so
hopefully.
A
We
yeah,
we
got
somebody
done
it.
I
think
chris
writes
his
hand.
E
All
right,
thank
you,
laura
for
okay,
yeah
yeah,
so
joe,
I
I
I
completely
understand
your
perspective.
I
I'm
looking
at
it
from
a
five
to
ten
year
program
of
research
which
we
need
funding,
and
so
what
we're
doing
now
is
not
just
trying
to
progress
the
hits
but
progress,
the
technology
platforms
that
we
can
then
insert
in
the
next
six
months
into
grants.
So
having
a
really
robust
crystal
system
is,
you
know,
would
be
a
big
tick.
E
You
know
for
as
many
of
the
mere
eye
gazers
as
possible
for
the
for
the
wider
program
as
well,
because
the
reality
is,
you
know
if,
if,
if,
if
muir
ligases,
if
we
can
crack
mirror
ligases
as
a
target,
that's
a
universal
target,
you
know,
and
so
we
we
need
we
need
to.
We
need
a
robust
crystal
platform
as
broadly
as
possible,
so
we
we're
trying
to
do
everything
on
all
fronts,
which
is
not
not
not
not
a
farmer
way.
E
I
know,
but
I'm
I'm
trying
to
think
of
how
to
how
to
how
to
keep
it
funded
as
well,
so
that
I
think
that
that's.
Why
we're
doing
that?
So
we
we're
going
to
fray
at
the
edges,
I'm
afraid
a
little
bit
on
speed
wise
and
we
have
had
two
project
students
who've
done
a
great
job,
characterizing
atp
dependence
of
the
hits
we've
got
so
far,
so
we
know
they're
on
target.
So
that's
the
new
information
on
mute
we
had
to
e
coli
dna.
E
We've
got
so
we'll
present
that
soon
so
yeah
we're
we're
we're
pulling
in
everybody.
We
can.
I
even
try
to
persuade
them
not
to
have
summer
holidays
and
come
back
and
do
some
more,
but
anyway
was.
F
Can
I
ask
you
a
question
about
about
something:
that's
come
up
before
about
the
idea
of
publishing
one
consistent
set
of
structures.
I
think
we've
previously
talked
about
the
idea
of
doing
sort
of
c
d
and
e
under
the
same
conditions,
with
the
same
well
under
the
same
conditions
from
the
same
species.
Right.
Is
that
what
you
were
talking
about
joe
getting
that
and
publishing
that.
D
Well,
yeah,
I
mean,
I
think,
that's
yeah,
I
guess
yeah,
I
hadn't
really.
I
guess
I'm
sure
I
have
the
answer
to
that.
Specifically
I
mean
you
know
somehow
you
have
to
make
a
story.
He
just
wanted
to
be
a
data
dump
right
and
so-
and
I
guess
I
was
thinking
at
this
point-
you
know
it
depends
on
when
you
you
know
what
you
want
to
do
with
ligand-bound
structures.
You
know
you
have
to
you
know
so
that
again,
that's
I
don't
have
the
answers
there
on
that
per
se.
D
I
just
feel
like
you
know,
both
you
know
laura.
You
know
the
warwick
team
and
the
and
the
seattle
group
have
now
generated
a
number
of
structures
that
aren't
available
and
you
can
put
them
in
the
pdb.
But
again
I
think
the
other
thing
from
a
grant
proposal.
You
know
having
showing
collaboration
having
a
publication.
D
A
Yeah,
so
I'm
trying
to
put
together
everything
that
we
have
in
terms
of
essays
and
crystals
and
all
that,
but
there
is
a
bit
of
inconsistency.
We
need
more
data
on.
You
know
on
the
every
hits
that
we
got
from
the
crystal.
I
think
we
need
some
essay
data
right.
If
not
it's
just
something
structures
and
not
really
well.
D
Yeah,
so
I
guess
I
wasn't
thinking
per
se
of
publishing,
I
mean
I
guess
the
question
becomes:
do
you
wait,
and
so
you
have
some
of
the
hits
or
I
was
thinking
just
you
know,
structures
with,
for
example,
that
you're
talking
about
like
the
uma
structure,
the
you
know,
adp
pcp
structure.
You
know
yarn
has
generated
the
pseudomonas
structure.
So
it's
it's
more
pulling
these
things
together
and
talk.
You
know
a
little
bit
about.
You
know
the
dynamics
now
so
now
you
know
how
do
you
get?
D
You
know
this
close
the
dynamics
of
the
close
and
open
forums,
what
what
actually
triggers
and
how
what
can
trigger
the
closed
confirmation
versus
the
open?
Obviously,
the
issues
you
know
with
apo,
it's
been
a
you
know,
quite
a
struggle.
I
would
say
right
getting
you
know
good
structures
with
of
of
apo
rear
ligases
right,
I
mean
in
general,
they're
they're.
Not
that
stable
is
what
I'm
hearing
right.
D
D
Right
right,
right
and
so
again
that
would
be
the
I
think
just
to
maybe
the
take-home
message
from
a
paper
is
that,
in
terms
of
for
drug
discovery
and
being
able
to
you
know,
drive
forward
with
you
know,
ligand-bound
structures,
you
need
to
be
able
to
stabilize
and
generate
these
these
close
confirmations.
D
So
that's
kind
of
you
know,
and
that
would
be
the
I
don't
know
I
mean,
there's
those
papers
already
out
there
about
the
dynamics
right
that
I've
shared
about.
You
know
the
dynamics
of
mere
ligases,
but
you
know
now
you
kind
of
have
some
more
experimental
evidence
of
different
of
of
a
broader
set
of
species,
whether
it's
your
scene,
your
d
and
your
e
anyway.
That's
I
don't
matt,
I
don't
really
have.
I
think
it
was
just
a
matter
of
you
know.
D
People
put
a
lot
of
time
in
and
I
would
thought
that-
and
I
think
especially
for
our
ss
gcid
folks,
who
have
been
so
gracious
with
their
support
to.
I
know
they
look
for
publications.
I
mean
they're
in
a
grant.
You
know
in
a
funding
situation
so
again
any
way
we
can
support
them
and
with
the
publication.
I
think
that's
a
good
thing
to
do.
C
Right,
and
also
if,
as
I
think,
we've
discussed
before
you
know,
yan
is
is
going
to
be.
You
know,
funding
john's
company
has
chosen
not
to
continue
on
with
the
ssg
id,
which
means
you
know
john.
He
may
volunteer
his
time.
I
don't
know,
but
if
we
want,
if
we
whatever
contribution,
we
want
from
yon
on
a
paper
like
that
needs
to
be
done
in
the
next
three
months.
So
I
definitely
think
that.
C
At
least
an
outline
in
the
materials
and
methods,
and
the
sections
that
you
would
want
to
include
from
yawn
would
be
much
better
done
right
now
than
you
know,
nine
months
or
a
year
from
now,
because
it's
going
to
be
hard
to
recreate
that
knowledge.
That
jan
has
what
would
be
impossible.
So
if
we
want
something
from
yawn,
we
need
to
get
it
now.
B
Screen
but
it's
shortly
right
if,
but
if
you
want
something
little
writing
up
materials
and
methods
or
something
like
that,
I
can
do
on
a
ferry
ride.
I'm
totally
happy
to
do
that
whatever
a
year
from
now.
B
A
E
E
We
don't
necessarily
have
to
get
through
all
the
ligand
stuff
as
well,
but
we
could
get
some
exam
exemplars
through
with
computational
modelling
as
to
what
as
to
what
impact
that
might
have,
and
maybe
we
take
a
couple
of
them
and
show
how
effective
or
ineffective
they
are
as
a
result,
just
as
a
kind
of
proof
of
principles
to
perhaps
indicating
as
to
why
things
have
not
worked
so
well
before
or
trying
to
understand.
E
C
D
C
Okay,
so
I
think
you
know,
maybe
we
should
have
a
side
meeting
or
something
that's
just
like
a
data
meeting
and
see
what
we
have
so
again
I
mean
that's.
I
guess
that's
what
we
did
today,
but
now
it
would
be
it'd,
be
nice
to
take
this
and
see
what
story
we
have
to
build.
Here
I
mean
I
the
first
go-round
is
always:
what
can
we
write
that
doesn't
require
any
more
experiments?
Do
we
not
think
that
we
have
anything
that
we
could
write
up
without
doing
any
more
experience
or
not.
C
And
I
would
like
to
I
guess
what
I'm
saying
is
can't,
let's
think
seriously
about
that.
Let's,
like
let's
test
that
question:
what
can
we
write
up
with
no
more
experiments,
yeah.
E
C
A
good
point,
and
if
we
don't
think
that
we
have
that
which
I
think
that
would
be
impossible,
but
of
course
it
all
depends
on
what
impact
the
world
journal.
You
want
to
go
to
or
something,
but
if
you
don't
have
something
that
you
really
want
to
publish
without
you
know,
because
in
the
end
I
think
the
decider
on
this
is
chris
dawson
right,
the
scene
would
be
the
senior
author
would
be
the
decider
on
the
what
we
data
we
include
or
not,
and
what
journal
we
go
to
say.
F
E
Exactly
and
for
me,
it
would
be
how
you've
used
the
structures
to
develop.
You
know
computationally
drived
inhibitors.
We
could
do
that
way,
potentially,
but
then
that
that
very
much
involves
joe.
D
D
You
know
that
that's
really
the
the
goal,
and
I
think
you
know
that
would
that
would
be
the
what
you
were
trying
to
show
at
some
point
right,
so
you're
trying
to
show
now
you
have
these
structures,
there's
similarity
again
from
my
side.
It
would
be
atp,
competitive
ones
and
and
then
just
the
dynamics.
D
And
then,
if
I
I
know
what
you're
saying
bart-
and
I
totally
agree,
but
if,
if
any
way
that
laura
sorry
laura,
if
you
know
if
you
can
get
an
exemplar
as
chris
was
saying,
you
know,
one
of
the
any
mean
hits
or
something
or
you
know.
I
assume
it's
coming
at
this
point
from
any
means
that
yeah
that
that
that
is
quote
shown
by
chemically
to
inhibit.
You
know
your
c
and
d
or
whatever
that,
and
that
would
be
kind
of
the
punch
line
at
the
end
right.
D
E
D
Structure,
you
know
so
if
you
could
get
the
crystal
structure
of
those
I
mean
that
would
be
like.
I
think
then
you're
talking
about
it.
You
could
maybe
get
a
more
impact
high
impact
journal,
otherwise
maybe
you're
sitting
in.
I
don't
know
what
you're
I'm
thinking
like
jmv
or
something
I
don't
know.
Yeah
yeah.
E
Yeah
we
know
they're
atp
competitive
as
well.
So
from
the
last
said
earlier,
the
last
experiments
we've
done
show
that
you
know
these
things
are
definitely
competitive,
so
yeah,
no
yeah,
no
pressure,
laura
just
crack
crank
those
out.
E
Mean
to
be
honest,
if
we
get
the
structures
of
those,
if
we,
if
we've
got
the
co-structures
of
those,
we've
got
a
whole
story
from
the
you
know,
the
you
know
the
structural
biology
of
the
structure,
the
design
and
the
inhibition.
I
would
I
wouldn't
I,
wouldn't
I
wouldn't
entitle
it
dual
targeting
I'd
entitle
it
multi-targeting,
because
I
I'm
aiming
for.
E
D
Sorry
about
sorry
about
ruining
your
vacation,
laura.
B
Well,
two
two
three
quarters
or
so
to
the
end
of
august.
That's
when
our
lab
work
needs
to
finish.
B
Yeah
I
will
collect
on
the
crystals
tomorrow
morning.
A
Okay,
whenever
you
have
the
data
you
know,
maybe
we
can
have
a
chat
again
and
see
what's
the
plan,
what
makes
it
try
next
yeah.
E
Good
and
like
bart's
heading
about
already
now
starting
to
us,
let's
just
start
to
assemble
what
we've
got
and.
D
D
A
D
B
Only
just
a
yeah
magnesium.
D
Okay,
so
then
I
guess
the
next
question
would
be.
You
know
if,
if
any
chance
that
you
know
if
you
get
crystals
to
try,
maybe
with
you
know
from
the
couple
of
those
az
compounds-
that
at
least
from
the
nano
dsf
looked
like
they
were
causing
shifts
and
that's
anita
backer.
Well,.
B
D
D
D
B
D
D
A
E
Just
we
have
an
inhibitor,
I
think
it's
one
of
the
was
it
one
of
the
aside
ones
that
hit
c
and
e,
but
not
d.
Is
that
one
of
matt's?
I
can't
remember
it's
one
of
max:
wasn't
it
was
on
a
maps
that
does
c
and
ironically
c
and
e,
but
not
d,
yeah,
on
the
on
the
on
on
the
enzyme.
I
say
so.
I
think,
there's
some
interesting.
C
B
B
C
A
Exactly
do
you
have
more
left.