gitter-badger/dimple

:large_blue_diamond: MX pipeline. Refinement and ligand screening.

dimple

Macromolecular crystallography pipeline for refinement and ligand screening.

Requires several programs from the CCP4 suite.

How it works

You provide data (merged mtz) and model (pdb) and tell the pipeline where it should dump the results:

$ dimple my.mtz apo.pdb output-dir

If you wish you can give more than one model or pdb code (only one of them will be used - the one with most similar unit cell):

$ dimple my.mtz apo.pdb my-other.pdb 4uqi output-dir

DIMPLE will do what it can to quickly return refined model, pointing to unmodelled electron density blobs - potential ligand sites.

Simplifying a bit: the pipeline runs macromolecular refinement after a few usual preparatory steps (I to F, choosing Rfree set, reindexing if needed). Sometimes it needs to run Molecular Replacement before refinement. And at the end it checks for unmodelled blobs - suspected ligands.

It's quick. Running time depends of course on data, model and computer, but about 3 minutes is typical. With MR it is usually 5-10 minutes, but from time to time much, much longer.

Options

DIMPLE has a lot of options (dimple -h lists all of them), but since the goal of the pipeline is to make things simple, we'll focus on one:

--slow (or -s for short) -- recommended if you are not in hurry. DIMPLE will take twice more time, spending it mostly on extra cycles of refinement. If this is still too fast, give this option twice

• to get 100 cycles of jelly-body refinement.

-M is also quite popular. It decides when MR should kick in: -M0 - always, -M1 - never, -M 0.4 - (default) if Rfactor after rigid-body refinement is above 0.4. Rfactor for this purpose is calculated only in data up to 3.5A.

Installation

DIMPLE is part of the CCP4 suite. All the work is done by other programs from the suite, which are run underneath. Most importantly refmac and phaser. So you need to have CCP4 installed.

To test the latest development version, clone this repository and run ./dimple/dimple.

Dimple comes with a little find-blobs utility. If you don't compile it, the version from the CCP4 suite will be used. Compilation requires clipper library which in turn requires mmdb2 and libccp4. You may either build everything from source or use conda to download binaries (with g++4 ABI). The latter can be done by installing miniconda and doing:

conda install -c mw clipper

Than build find-blobs pointing where the required libraries are:

cmake -D CMAKE_PREFIX_PATH=$HOME/miniconda2 .
make

No need for make install - the binary landed in the same directory as the python scripts and dimple will use programs from here in preference to the ones from $CCP4/bin.

If it doesn't work - see the contact methods below.

Selected Details

reindexing (Pointless) - if the data and model are in compatible but different spacegroups, we change the spacegroup in the MTZ file. We also check all possible settings - Pointless calculates structure factors from the model and compares the CC on E^2 to find the best matching settings, reindexing data if necessary. In some cases this steps saves as a couple minutes by avoiding MR.

free reflections - Rfree statistic depend to some degree on how lucky is the pseudo-random set of free flags. To eliminate this luck factor when comparing different data collection one may want to use the same set of free flags. It is possible by passing external set of reference flags (option --free-r-flags), but we wanted to do even without the reference file. This was implemented by generating the same free set for the same pdb file and should work if the space group is the same and the resolution is below 1A (we had to pick arbitrary limit).

scoring blobs - it is rather simplistic now, we need to work on it

generating pictures - we have an option (-f) to generate static images (PNG or JPEG) of the blobs. They are used by SynchWeb in DLS. Pictures are generated with Coot+Raster3d - this combines the familiar look and feel of Coot with nicer graphics and headless rendering.

Comments?

Any thoughts, comments or feedback is welcome. If it doesn't work as expected or doesn't work at all - let us know asap. Feel free to use the issue tracker here or email CCP4 helpdesk or email [email protected].

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Made in Diamond Light Source and in CCP4-Harwell.