Dear members of the structural biology community,
It is with great pleasure that I announce the release of version 1.0b1
of ISOLDE, a new, free for academic/nonprofit use, environment for
interactive rebuilding of macromolecular models against low-medium
resolution experimental crystallographic or cryo-EM maps.
A paper describing ISOLDE is online at
http://scripts.iucr.org/cgi-bin/paper?S2059798318002425, and you can
also get an overview from my demonstration video at
https://www.youtube.com/watch?v=limaUsNAVL8.
In brief, though, ISOLDE is designed to help overcome the substantial
challenge involved in building high-quality models into “difficult” maps
(e.g. those with worse than 3Å resolution) by re imagining the task as
one akin to interacting with a real, “living” molecule. At its heart is
the use of interactive molecular dynamics: all atoms feel van der Waals
and electrostatic interactions with their neighbours as you interact
with them, avoiding clashes and constantly settling towards their
nearest low-energy state. In addition to this, ISOLDE helps interpret
what you're looking at by performing real-time rotamer, Ramachandran and
peptide plane validation, flagging up potential problems directly on the
model to give you instant feedback on the results of your actions.
Specific features:
- support for protein, nucleic acid, water and some small molecules/ions
(with substantially expanded support to come in later versions)
- start an interactive simulation covering anything from a few residues
to your entire model (depending on your hardware) at the click of a
button
- “always-on” validation updates every time coordinates change (results
are shown directly as markup on the model itself, and also accessible
via more traditional tables/plots)
- Interactively apply peptide plane or cis/trans flips and add/remove
position, distance, rotamer and secondary structure restraints via a
simple graphical interface
- Smoothly shift any continuous stretch of backbone forward/backward
along the chain to easily recover from register shift errors
- Save a checkpoint in a running simulation and return to it with a
button click, allowing you to experiment with tricky regions without
fear
- Real-time visualisation of crystal symmetry contacts: when the master
atoms move, they move.
- One-button masking of maps to cover any arbitrary atom selection –
particularly useful for diagnosing large-scale problems.
- Extensive GUI and API documentation, available by clicking the “Help”
button in the ISOLDE GUI window.
ISOLDE is built as a plugin to UCSF ChimeraX
(http://preview.cgl.ucsf.edu/chimerax/download.html) and is currently
available for modern Linux distros and MacOS, and can be installed from
within ChimeraX via its ToolShed (Tools/More Tools...). It should run on
any Linux version that supports ChimeraX itself. NOTE: due to some
recent changes in the ChimeraX API, the current build will only work
with the ChimeraX 0.6 release (not the version 0.7 daily builds).
In terms of hardware, ISOLDE is designed based on the understanding that
not everybody has access to high-performance computing facilities, so
its minimum requirements are as modest as possible. The most important
requirement is a GPU capable of OpenCL 1.2 or CUDA processing. My
“go-to” machine for performance testing is a 2016-model gaming laptop
equipped with a Nvidia GTX 1070 GPU – this achieves ~20 coordinate
updates and >30 graphics updates per second with live validation on the
included 229-residue demo model, indistinguishable from (or slightly
faster than) my Xeon workstation. At the other end of the scale, it runs
at usable speeds on my MacBook Air for simulations of a few dozen
residues, sufficient for many tasks.
I hope you find it useful, and enjoy using it as much as I've enjoyed
making it. The MolProbity score to beat on the demo model is 1.02 (after
refinement in your favourite package – ID is in the PDB header so you
can download reflections from the wwPDB), and bonus points if you can
identify the mystery ligand (I can't). If you recognise it as your model
I apologise – I picked it out at random, I swear!
Best regards,
Tristan
