Re: [ccp4bb] [EXTERNAL] Re: [ccp4bb] Modeling ATP/ADP

[Oleg Kovalevskiy - UKRI STFC]

Dear Reza,

We had a case when two phosphate ions and magnesium ion have been bound to the 
ATP-binding site (300mM sodium phosphate in the crystallisations conditions). 
However, your ATP/ADP may not have full occupancy and therefore electron 
density might be lower. You may consider calculation of a blurred map (bring up 
contributions from low-resolution terms) and see whether there is any density 
for the nucleotide.
But first of all I would calculate omit map (without ligand) and would start to 
worry if there is no density for nucleotide part.

All the best,
Oleg

--
Dr Oleg Kovalevskiy
CCP4 team
UKRI Science and Technology Facilities Council
Rutherford Appleton Laboratory
Harwell Campus
Didcot, Oxfordshire
OX11 0QX
UK

From: CCP4 bulletin board  on behalf of Reza Khayat 

Reply to: Reza Khayat 
Date: Thursday, 23 July 2020 at 21:13
To: ccp4bb 
Subject: Re: [ccp4bb] [EXTERNAL] Re: [ccp4bb] Modeling ATP/ADP


Tried the homologues thing. There are homologues and I've done the fitting, but 
this is what I consider to be subjective. I'm certain the referee will ask: 
Given the quality of density for the nucleotide, how certain are the authors 
that a different fit is not possible? Have other fit poses been considered?



Reza


Reza Khayat, PhD
Assistant Professor
City College of New York
Department of Chemistry and Biochemistry
New York, NY 10031

From: CCP4 bulletin board  on behalf of Jon Cooper 
<488a26d62010-dmarc-requ...@jiscmail.ac.uk>
Sent: Thursday, July 23, 2020 1:07 PM
To: CCP4BB@JISCMAIL.AC.UK
Subject: [EXTERNAL] Re: [ccp4bb] Modeling ATP/ADP

Hello, do you have any homologues in the PDB with ATP, etc, bound as a guide? 
Coot is pretty good at fitting known ligands, and unknown ones, too!


 Original Message 
On 23 Jul 2020, 17:53, Reza Khayat < rkha...@ccny.cuny.edu> wrote:


Hi,



Can folks suggest programs for objectively docking ATP/ADP molecules into 
density? Our density is not so good, probably because of occupancy, and we'd 
like a less subjecting approach for modeling. Thanks.



Best wishes,
Reza


Reza Khayat, PhD
Assistant Professor
City College of New York
Department of Chemistry and Biochemistry
New York, NY 10031



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[ccp4bb] AW: Modeling ATP/ADP

[Schreuder, Herman /DE]

Hi Reza,

Since nobody answered your question so far, I will do it now:
In our hands, ArpWARP autoligand is still the best program to automatically 
dock ligands into electron density maps. Alternatively, on could also try 
Rhofit from Global Phasing or some other docking program.

However, the results of even the best docking program are still inferior to the 
results an experienced crystallographer can achieve. As others said, here you 
will need all the information you can get hold of:

  1.  Superimpose homologous structures and look if the ATP position correlates 
with your electron density.
  2.  Fit the ATP in every possible pose, refine each one and look which one is 
the best.
  3.  Look if the binding mode makes sense, e.g. no highly charged phosphates 
in hydrophobic pockets.
  4.  Look if the bad electron density makes structurally sense, e.g. density 
disappearing after a freely rotatable bond, but not in rigid parts etc.
  5.  Use your scroll-wheel to scroll up and down the contour level of your 
electron density map: scrolling up may reveal the phosphate positions, since 
they should have the highest electron density; scrolling down may reveal parts 
of the molecule with low electron density due to low occupancy.
  6.  Keep in mind that you may have a mixture of ATP and ADP bound, causing 
disordered maps.

Good luck!
Herman

Von: CCP4 bulletin board  Im Auftrag von Reza Khayat
Gesendet: Donnerstag, 23. Juli 2020 18:53
An: CCP4BB@JISCMAIL.AC.UK
Betreff: [EXTERNAL] [ccp4bb] Modeling ATP/ADP


EXTERNAL : Real sender is 
owner-ccp...@jiscmail.ac.uk


Hi,



Can folks suggest programs for objectively docking ATP/ADP molecules into 
density? Our density is not so good, probably because of occupancy, and we'd 
like a less subjecting approach for modeling. Thanks.



Best wishes,
Reza


Reza Khayat, PhD
Assistant Professor
City College of New York
Department of Chemistry and Biochemistry
New York, NY 10031



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Re: [ccp4bb] RES: [ccp4bb] Macromolecular Crystallography workshop in South America 2020

[Marko Hyvönen]

Very well said Frank.
And if the meeting really needs (why?) that regular dude to appear, they can 
give a 20 min intro (same slides as last year, no doubt) and share the lectern 
with a  student / postdoc who presents the new science.

Marko

On 24 Jul 2020, 07:17, at 07:17, Frank von Delft  
wrote:
>Thanks Stephen for reminding me there's a point no-one raised at the
>time:
>
>There are two sets of people that have agency in this:  1) the
>organisers, and 2) the ones that get the invites.
>
>Group 1 already have a tough job:  organising a meeting is a pile of
>work - so go easy on them.  (Or organise one yourself, and have fun.)
>
>
>It's Group 2 that is by far the largest and most powerful:  we who are
>in it really do not need to accept /every/ /single /invitation; it is
>not only in our power but also our duty (on many levels) to send group
>members or collaborators instead - even just occasionally can already
>make a difference.
>
>And then suddenly we discover all these female and minority and other
>under-priviledged speakers that lie in our gift to advance - and even
>better, we get to do some mentoring while we're at it, not least to
>teach that most insidious skill that we the priviledged were handed for
>
>free, namely how to wear our priviledge lightly by taking it for
>granted.
>
>(I cannot of course claim this insight as my own, or even claim to be
>particularly consistent at it - so I must thank group members and
>colleagues and spouses for making the penny eventually drop by holding
>my toes to the fire.)
>
>
>But yes, organisers:  you /can/ ask your invitees to help you, by
>reminding them that you're not in fact interested /in //them as
>speakers, /just in having their work presented at your meeting -- so
>could they please suggest someone suitable.
>
>phx.
>
>
>
>
>
>
>
>
>
>
>
>
>
>On 23/07/2020 10:21, Stephen Curry wrote:
>> It has been on my mind to respond to this thread since I was made
>aware of it in late February. Not because I regard myself as any sort
>of sage on these matters, but because I received a phone call from
>someone asking me to speak out. This person did not want to give her
>name and or to go into specific details, but it was clear that the
>issue matters a great deal to her. Unfortunately, she called while I
>was in the midst of trying to do three other things, so I did not give
>our discussion all the attention it deserved and that is a matter of
>some regret. I hope I can make some small amends by contributing here.
>> First off, I make no pretence at expertise. And nor am I going to
>pick up on individual comments, I just want to make some general
>observations and suggestions.
>>
>> It is good to see this discussion happening within the CCP4 community
>and to see so many people engage. The question of female representation
>in academic workshops and conferences is a live one and one where we as
>a community must do better. This is not simply a matter of suggesting
>that more women should step forward to volunteer their services. And
>nor would I suggest having women-only events, except perhaps as a
>provocative experiment to give those of us in the majority (i.e. white
>men) a little taste of what it feels like to be excluded.
>>
>> To my mind the key here is to recognise the systemic biases and
>accept that we all have a responsibility to fix the system. We can’t
>simply leave ‘solving the problem’ to those in the under-represented
>groups (whether they be women, people of colour, disabled people etc).
>It is tiring for women (and other minoritized groups) to keep having to
>point out what is wrong;  that burden in itself is part of the
>structural bias. And nor should we ignore or silence their concerns
>because we have not seen or experienced them ourselves.
>>
>> Listening has to be a central part of the process, or ‘people talking
>to people’ as Atul Gawande puts it in an insightful piece about how to
>get people to see things from a different perspective
>(https://www.newyorker.com/magazine/2013/07/29/slow-ideas). This isn’t
>always going to be easy, but if we are really committed to including
>all people of talent within the scientific community and enjoy the
>intellectual fruits (and justice…) of diversity, we need to be prepared
>for what Margaret Heffernan (another of my favourites) might call
>‘creative conflict’
>(https://www.ted.com/talks/margaret_heffernan_dare_to_disagree?language=en).
>>
>> Of course, tools and processes will also help. I agree with those who
>suggest that we should be proactive about seeking out women and other
>under-represented folks when looking for workshop tutors or conference
>speakers (or new people to hire). To that end, at Imperial we have
>introduce a new conference policy (which others are free to copy – that
>is in part how we constructed it ourselves -
>https://www.imperial.ac.uk/equality/governance/policies/conference-policy/).
>This sets out not only a code of conduct but also guidance on how to
>ensure better 

Re: [ccp4bb] RES: [ccp4bb] Macromolecular Crystallography workshop in South America 2020

[Frank von Delft]

Thanks Stephen for reminding me there's a point no-one raised at the time:

There are two sets of people that have agency in this:  1) the 
organisers, and 2) the ones that get the invites.


Group 1 already have a tough job:  organising a meeting is a pile of 
work - so go easy on them.  (Or organise one yourself, and have fun.)



It's Group 2 that is by far the largest and most powerful:  we who are 
in it really do not need to accept /every/ /single /invitation; it is 
not only in our power but also our duty (on many levels) to send group 
members or collaborators instead - even just occasionally can already 
make a difference.


And then suddenly we discover all these female and minority and other 
under-priviledged speakers that lie in our gift to advance - and even 
better, we get to do some mentoring while we're at it, not least to 
teach that most insidious skill that we the priviledged were handed for 
free, namely how to wear our priviledge lightly by taking it for granted.


(I cannot of course claim this insight as my own, or even claim to be 
particularly consistent at it - so I must thank group members and 
colleagues and spouses for making the penny eventually drop by holding 
my toes to the fire.)



But yes, organisers:  you /can/ ask your invitees to help you, by 
reminding them that you're not in fact interested /in //them as 
speakers, /just in having their work presented at your meeting -- so 
could they please suggest someone suitable.


phx.













On 23/07/2020 10:21, Stephen Curry wrote:

It has been on my mind to respond to this thread since I was made aware of it 
in late February. Not because I regard myself as any sort of sage on these 
matters, but because I received a phone call from someone asking me to speak 
out. This person did not want to give her name and or to go into specific 
details, but it was clear that the issue matters a great deal to her. 
Unfortunately, she called while I was in the midst of trying to do three other 
things, so I did not give our discussion all the attention it deserved and that 
is a matter of some regret. I hope I can make some small amends by contributing 
here.
First off, I make no pretence at expertise. And nor am I going to pick up on 
individual comments, I just want to make some general observations and 
suggestions.

It is good to see this discussion happening within the CCP4 community and to 
see so many people engage. The question of female representation in academic 
workshops and conferences is a live one and one where we as a community must do 
better. This is not simply a matter of suggesting that more women should step 
forward to volunteer their services. And nor would I suggest having women-only 
events, except perhaps as a provocative experiment to give those of us in the 
majority (i.e. white men) a little taste of what it feels like to be excluded.

To my mind the key here is to recognise the systemic biases and accept that we 
all have a responsibility to fix the system. We can’t simply leave ‘solving the 
problem’ to those in the under-represented groups (whether they be women, 
people of colour, disabled people etc). It is tiring for women (and other 
minoritized groups) to keep having to point out what is wrong;  that burden in 
itself is part of the structural bias. And nor should we ignore or silence 
their concerns because we have not seen or experienced them ourselves.

Listening has to be a central part of the process, or ‘people talking to 
people’ as Atul Gawande puts it in an insightful piece about how to get people 
to see things from a different perspective 
(https://www.newyorker.com/magazine/2013/07/29/slow-ideas). This isn’t always 
going to be easy, but if we are really committed to including all people of 
talent within the scientific community and enjoy the intellectual fruits (and 
justice…) of diversity, we need to be prepared for what Margaret Heffernan 
(another of my favourites) might call ‘creative conflict’ 
(https://www.ted.com/talks/margaret_heffernan_dare_to_disagree?language=en).

Of course, tools and processes will also help. I agree with those who suggest 
that we should be proactive about seeking out women and other under-represented 
folks when looking for workshop tutors or conference speakers (or new people to 
hire). To that end, at Imperial we have introduce a new conference policy 
(which others are free to copy – that is in part how we constructed it 
ourselves - 
https://www.imperial.ac.uk/equality/governance/policies/conference-policy/). 
This sets out not only a code of conduct but also guidance on how to ensure 
better representation among speakers and panellists at workshops and 
conferences. Those of us in the majority who are accustomed to receiving 
invitations to speak have a crucial role to play here in testing the 
organisers’ commitment to diversity. I have a personal policy of not appearing 
on all-male panels or line-ups of speakers. I am now also trying to