"The XChemExplorer graphical workflow tool for routine or large-scale protein-ligand structure determination."

Acta Crystallogr D Struct Biol. 2017 Mar 1;73(Pt 3):267-278. (https://doi.org/10.1107/S2059798316020234)

XChemExplorer (XCE) is a data-management and workflow tool to support large-scale simultaneous analysis of protein-ligand complexes during structure-based ligand discovery (SBLD).

The user interfaces of established crystallographic software packages such as CCP4 [Winn et al. (2011), Acta Cryst. D67, 235-242] or PHENIX [Adams et al. (2010), Acta Cryst. D66, 213-221] have entrenched the paradigm that a 'project' is concerned with solving one structure. This does not hold for SBLD, where many almost identical structures need to be solved and analysed quickly in one batch of work. Functionality to track progress and annotate structures is essential.

XCE provides an intuitive graphical user interface which guides the user from data processing, initial map calculation, ligand identification and refinement up until data dissemination. It provides multiple entry points depending on the need of each project, enables batch processing of multiple data sets and records metadata, progress and annotations in an SQLite database.

Operating Systems:

• Linux
• Mac OSX

Prerequisites:

• CCP4 version 7.0 (or higher)
• PHENIX (optional, but recommended)

Please note: The recommended installation process, described below, includes an install of CCP4. This is so that we know that our code works with the version of CCP4, rather than your system version, making user support much easier

Potential solutions:

a) Partition your hard drive and install a light-weight version of linux, such as Ubuntu: https://www.ubuntu.com/download/desktop

b) Install Ubuntu (or other) on a USB drive, and boot from that: https://tutorials.ubuntu.com/tutorial/tutorial-create-a-usb-stick-on-windows#0 (NB: This will require a huge USB stick or external hard drive - ccp4 is a large package)

c) VirtualBox - emulate a linux environment on your Windows desktop: https://www.virtualbox.org

1. Clone the github repository onto your machine with:

git clone https://github.com/xchem/XChemExplorer

2. Change directory into the repository:

cd XChemExplorer/

3. Run the test_build.sh script (this is currently only included for bash, but you can view the steps within the script and modify it as you please for other shells):

./test_build.sh

4. To execute, run the XChemExplorer_local.sh script

./XChemExplorer_local.sh

(We recommend you add an alias to your bash profile to do this)

alias xce="<full_path_to_local_git_repository>/XChemExplorer_local.sh"

NX latency is a killer when trying to do anything graphical, like model building during pandda.inspect or during refinement. So instead use Filesystem in Userspace (FUSE), which mounts Diamond’s disk from your computer using the ssh protocol. All you need is root privileges, or bribe your IT team.

1. Setup fuse (requires admin rights) Install FUSE (http://github.com/libfuse/libfuse)

Centos:

sudo yum install fuse-utils sshfs

Ubuntu:

sudo apt-get install sshfs

See https://gist.github.com/cstroe/e83681e3510b43e3f618 for details. FUSE is also available for Mac. Avoid building from source unless you really have to.

Create a /dls mount point and give your user ownership:

sudo mkdir /dls
sudo chown <yourUID>:<yourGID) /dls

2. Mount the Diamond filesystem

When you need it, run this from your own user account:

sshfs -o reconnect <your_fed_id>@nx.diamond.ac.uk:/dls /dls
e.g. sshfs -o reconnect zqr16691@nx.diamond.ac.uk:/dls /dls

(Recommended): make your ssh client to keep the link alive by editing ~/.ssh/config and adding these lines:

ServerAliveInterval 15
ServerAliveCountMax 3

(The “reconnect” option is meant to do this too, but it slows down and eventually drops it anyway.)

3. Fire up XCE

cd <your-labxchem-visit-dir>

e.g. cd /dls/labxchem/data/2017/lb18145-3/processing

/dls/science/groups/i04-1/software/XChem/xce

(See Note 1 below.)

4. When you’re done, unmount the file system

fusermount -u /dls

1. Launching XCE this way avoids insane installation issues, because it runs the software directly off Diamond’s drives, i.e. it’s exactly what you use if physically at Diamond or through NX. This is therefore supported. The trade-offs are currently (but we’re trying to fix):

a. It takes a very long time (up to 10 minutes in the UK and up to an hour(!) in North America) to launch XCE and pandda.inspect. After that they are fully responsive.

b. The xce-coot plugin does not always work, due to a library mismatch.

2. IF YOU KNOW WHAT YOU’RE DOING and really hate (!) the lag on startup:

a. install XCE locally: https://github.com/xchem/XChemExplorer

b. update your PanDDA installation (the ccp4 version is outdated):

ccp4-python -m pip uninstall panddas
ccp4-python -m pip install pip –upgrade
ccp4-python -m pip install numpy –upgrade
ccp4-python -m pip install panddas

(Note, this is not supported – you really are on your own! Recommended only for geeks.)

3. If your IT team doesn’t want to help you, try setting up a virtual machine – then you have root permissions and can do whatever you like. Performance ought to be okay.

XChemExplorer is licensed under the MIT license.