Hi all,
For those still lucky enough to be working on molecular model building
during this crisis, I've just pushed ISOLDE 1.0b5 out to the ChimeraX
ToolShed (to work with the ChimeraX 0.93 release version - download from
http://preview.cgl.ucsf.edu/chimerax/download.html#release, then install
ISOLDE from within ChimeraX via Tools/More Tools...). While development
has been a little light since version 1.0b4 due to travel in February
and then, well... everything since, there are a few new features and
bug-fixes worth downloading for:
- Perhaps the biggest improvement isn't actually mine - thanks to some
stellar work by Tom Goddard at UCSF, ChimeraX's ribbon drawing is now
ten times faster than before. Particularly for those working with very
large models, this drastically reduces the lag time upon finishing an
interactive simulation and returning to the default display mode.
- I've done some optimisations to the methods for choosing the initial
map contour levels and the MDFF coupling constant (how strongly the map
"pulls" on the model during simulations). They're now about 20 times
faster, removing most of the delay on initial preparation of a model for
ISOLDE.
- If you're lucky enough to be working on a multi-GPU machine, you can
now explicitly specify the GPU to use for simulations with the command
"isolde set gpuDeviceIndex {a number}" (you may need to experiment to
work out which GPU is which)
- You can adjust the number of simulation steps between GUI updates with
"isolde set timeStepsPerGuiUpdate". This is particularly useful for
slower GPUs - your simulation won't actually run faster, but your
experience of it will be much smoother. The default value of 50 works
well for high-end GPUs; for (for example) light-weight MacBook GPUs a
value of 10 may be more suitable. Performance curves for a few of the
machines available to me can be found at
https://isolde.cimr.cam.ac.uk/performance-benchmarks/.
- The command "clipper symmetry #{model number}" will draw a unit cell
with all rotational symmetry and screw axes (mirror symmetry is not yet
handled). The depiction is still a work in progress, but the
fundamentals are there.
- While not new to 1.0b5, a reminder that since 1.0b4 ISOLDE is fully
compatible with ChimeraX's session save/restore. The command "save
{filename}.cxs" will save your current session (including your model(s),
all custom restraints, maps, weightings and visualisation state) to a
file which can be reopened on the same or another machine to pick up
exactly where you left off.
Known bug: (seemingly only) on Linux machines, certain links to the help
files (e.g. by typing "usage isolde" on the command line and then
clicking the "isolde adjust distances"link in the log) sometimes cause
segmentation faults if the help browser is not already open, crashing
ChimeraX. This appears to be a bug in the Qt 5.12 web browser
implementation, but so far has proven near-impossible to isolate. To
avoid it, simply make sure the help browser is open (Help/User Guide)
before clicking any links in the log.
I very much hope you find it useful.
Stay healthy!
Tristan
Dear all,
Last week I posted the message below, suggesting an open science approach to ensure that there will be no unnecessary delays in the determination of crystal structures related to COVID-19, whether they’re from the SARS-CoV-2 virus, interacting host proteins, or complexes. Working together, and combining expertise in data analysis, structure determination and computational modelling, we believe we can greatly accelerate progress on difficult structures.
Since last week we’ve chosen a platform, Microsoft Teams, to coordinate the effort, created a new Team and built the bare bones of a site ready for new targets. (For those who prefer other collaboration platforms such as Slack or Zulip, they might well have advantages but I had easy access to the Teams infrastructure and we’re already using it for working from home.)
If you believe that you can bring expertise to this initiative and you’re willing to share your insights and any promising results immediately with others, please get in touch and I’ll add you to the team.
If you have diffraction data for a target structure for this initiative, please send an email to me, to Massimo Sammito (mds83(a)cam.ac.uk) and to the CASP organisers (casp(a)predictioncenter.org). Either Massimo or I will add you to the team, upload the target data, links and other information and send an alert to everyone who has registered.
Best wishes,
Randy Read
===========
The Covid-19 crisis is bringing out the best in the communities we belong to, with many people giving deep thought to how we can use our skills to help. On the crystallography bulletin boards we've seen offers to help in solving Covid-19-related structures that prove difficult, offers to help with improving protein stability, suggestions that the deposition of raw diffraction images would allow the community to help get the best possible version of any relevant structure, and requests to share bioinformatics analyses and predictions of what are the most interesting targets.
We're writing to suggest an additional way that the community can help to accelerate progress in the structural understanding of Covid-19. The CASP (Critical Assessment of Structure Prediction) organisers have recently launched an initiative to mobilise the structure prediction community to predict and refine 3D structures of SARS-2-Covid proteins and relevant complexes that either have unknown structure or are non-trivial modelling targets:
http://predictioncenter.org/caspcommons/index.cgi.
Note that the models will be refined much more extensively than typically done in a normal CASP round, which should make them even better than the impressive results seen in recent years.
We would like to build on this initiative, and the enthusiasm this has revealed in the prediction community, to help to accelerate the determination of structures needed for a molecular-level understanding of Covid-19. Structure prediction has reached a level of maturity where predicted ab initio models and distant homology models can be accurate enough to solve new structures by molecular replacement. The best way to bring the prediction and experimental communities together to exploit these developments and accelerate progress is to embrace an open science approach. To that end, we propose the following:
* If you have diffraction data involving a SARS-2-Covid protein, a host protein relevant to pathogenesis or a complex, but you are not immediately able to solve the structure, contact the CASP organisers (casp(a)predictioncenter.org) with the sequence(s) of the construct(s) that went into the crystallisation drop. If relevant predictions have already been made, any unreleased models will be released at this point (along with predictions of local accuracy). If proteins in your crystals are not already modelling targets, the CASP organisers will consider them as potential new targets for the modelling community.
* We all want the fastest possible progress on scientific understanding of Covid-19, and this can best be achieved by completely open science. On a number of occasions at crystallographic computing schools and workshops, we have seen extremely difficult structures yield to the combined expertise of a number of developers and "power users" of the software, none of whom knew how to solve every problem that arose. Even before CASP models are available, some other crystallographer may find a way to solve the structure! So it would be ideal if the sequence information you provide to the CASP organisers was accompanied by a DOI or URL pointing at the diffraction data, preferably in the form of raw images as well as integrated data. Data from different crystal forms or poorly isomorphous crystals can also be incredibly valuable. Openness should go both ways, so people who wish to access these data will be asked to agree to immediately release any positive results, even if these fall short of a full structure solution, so that others can build on them.
Best wishes,
Randy Read (in cooperation with the CASP organisers)
-----
Randy J. Read
Department of Haematology, University of Cambridge
Cambridge Institute for Medical Research Tel: +44 1223 336500
The Keith Peters Building Fax: +44 1223 336827
Hills Road E-mail: rjr27(a)cam.ac.uk
Cambridge CB2 0XY, U.K. www-structmed.cimr.cam.ac.uk
Dear All,
My colleague and I are troubleshooting a Phaser run that her Phenix was not able to solve but mine was. We both use the Graphical User Interface, and we both use the current version, Phenix 1.17.3644 Her log file shows “ELLG TARGET 120” and “RFACTOR CUTOFF 35.00”. If these settings are the reason one run gave the right solution and the other didn’t, how do we access and change these settings?
I attached both the log files. Right.log gave the right solution, Wrong.log gave the wrong solution.
Many thanks,
Rachel Werther
Rachel Werther / Research Technician III / Stoddard Lab / Basic Sciences / Fred Hutchinson Cancer Research Center / rwerther(a)fredhutch.org<mailto:[email protected]> / 206-667-4066
All - last week's call for compound designs to the CoV-2 main protease
(https://covid.postera.ai/covid)
elicited an astonishing response... (I confess I was quite taken aback.)
I just realised I should let this BB know the second call for designs is
now open. *Deadline is tomorrow 23:59 PST (April 2nd). *(Apologies for
those that weren't following on twitter.)*
*Two things:
* we're asking for designs especially focusing on covalent inhibitors
(read more here
<https://discuss.postera.ai/t/screening-cascade-fast-track-and-regular-track…>)
* the most convincing designs will be fast-tracked by spending more
money to cut several weeks off the testing (read more here
<https://discuss.postera.ai/t/screening-cascade-fast-track-and-regular-track…>)
Happy designing!
Frank
