Applications are particularly welcomed from early and mid-career UK researchers.

You must be based at a UK research organisation eligible for UK Research and Innovation (UKRI) funding.

The full economic cost (FEC) of your project can be up to £602,500. UKRI will fund 80% of the FEC (£482,000).

Projects must start on 1 February 2027 and last for up to 24 months.

https://www.ukri.org/opportunity/next-generation-artificial-intelligence-ai-explainable-ai/?utm_medium=email&utm_source=govdelivery

The latest of these challenges is the OpenADMET PXR Blind Challenge. The challenge is in two parts an Activity Dataset of over 11,000 molecules that can be used to produce machine learning models. In addition there is a Structure dataset containing 184 new X-ray structures with small molecules bound together with In addition, 68 structures from the PDB.

The pregnane X receptor (hPXR) is the major determinant of CYP3A gene regulation by drugs and other xenobiotics. In addition, PXR mediates induction of P450s 2B6, 2C8/9, and 3A4, as well as the drug transporters MDR1, organic anion transporting polypeptide C, bile salt export protein, and multidrug resistance-associated protein 2.

The binding site is large and hydrophobic with several important hydrogen bonding interactions. There may be multiple binding conformations. Similar to CYP3A pharmacophore, many (but not all) CYP3A substrates/inhibitors are also CYP3A inducers.  As shown below many structural classes can be accommodated by the receptor

Whilst 184 X-ray structures of the receptor with ligand bound are available, navigating between the structures is a significant challenge. Fortunately, Manish Sud has done much of the heavy lifting for you and has generated a PyMOL session file named OpenADMET-PXR-Crystal-Structures-Aligned.pse.zip (258M). It provides a ligand centric hierarchical views to visualize the data. The B factor visualization is also available in the PyMOL session file.

The uncompressed file is fairly large (1.25 GB) so will take a little while to load but once loaded it provides a means to easily compare structures. This is a fantastic resource.

There are issues with this system, the same file type e.g. .sdf can be opened and viewed by a number of applications, and a given application can open multiple different file types, and different apps might also provide QuickLook extensions. Whilst you can turn off a particular QuickLook extension in System preferences, this eliminates QuickLook views for every file type registered for that extension. I’ve not found a way to assign a particular file type to a particular QuickLook extension.

There is also the issue of file types, macOS uses a combination of Uniform Type Identifier (UTI) and file extensions. Unfortunately this system means that you can have a single file type with multiple entries in the database of UTI.

The day after the review was posted I got a comment on BlueSky

Recently found QuickLookDoctor for setting QuickLook extension preferences. markedapp.com/ql/doctor/

I quickly downloaded it and it is an invaluable tool for setting which Quick Look extension is used for which file type.

https://raymol.io

A Metal rendering engine replaces OpenGL, adding real-time shadow mapping, ambient occlusion, and order-independent transparency at interactive frame rates. On supported Apple Silicon, hardware ray tracing is available for higher-quality lighting. The direct-download and Homebrew builds also include the built-in MCP server, so Claude can drive Raymol. The Mac App Store build leaves that out because App Store sandboxing doesn’t permit it — the engine, rendering, and every other feature are identical.

https://prolif.readthedocs.io/en/stable

It can be installed using Conda

conda install -c conda-forge prolif

Burette is available on GitHub https://github.com/SergeiNikolenko/Burrete or can be installed using Brew

brew tap SergeiNikolenko/burette
brew install --cask burette

You may need to trust before downloading

brew trust --cask sergeinikolenko/burette/burette

This will install Burette in your applications folder. If you then click on Burette you will get a message that it was downloaded from a non AppStore site and has not been checked for malware. If you are happy to use it you need to go to the Privacy and Security settings and authorise it. The App will be registered and two extensions will then be installed.

You are now set to use Burette in two ways:

• Finder previews: select a molecular file in Finder and press Space.
• Desktop workspace: open Burrete directly to inspect files in tabs, browse project folders, search commands and structures, sketch molecules, review collections, and send files to external chemistry tools.

Using Burette

Select a file in the finder, in this case a file containing a SMILES string with the extension .smi and hit the space bar. A popup window opens up showing the rendered structure.

If the file contains multiple SMILES strings all the structures are rendered and can be displayed on individual cards or as a table.

If the SDF contains associated data fields they can also be displayed by clicking the “Properties” button.

Other file types can also be previewed for example pdb files, in this case you can mouse over the display to highlight portions of the display for example the ligand. The structures can be smoothly rotated in 3D using the Mouse.

There are issues with this system, the same file type e.g. .sdf can be opened and viewed by a number of applications, and a given application can open multiple different file types, and different apps might also provide QuickLook extensions. Whilst you can turn off a particular QuickLook extension in System preferences, this eliminates QuickLook views for every file type registered for that extension. I’ve not found a way to assign a particular file type to a particular QuickLook extension.

There is also the issue of file types, macOS uses a combination of Uniform Type Identifier (UTI) and file extensions. Unfortunately this system means that you can have a single file type with multiple entries in the database of UTI. You can examine this using utitool (https://github.com/smittytone/utitool). Examining sdf we get

(base) chrisswain@Mac-Studio ~ % utitool -e sdf
UTI information for file extension .sdf
1. com.mdli.sketchfile
   Content type: MDL SDfile
   MIME types registered: chemical/x-mdl-sdfile
   UTI is registered with the system
2. com.revvity.external.sdf3
   Content type: MDL SDfile V3000
   MIME types registered: chemical/x-mdl-sdfile
   UTI is registered with the system
3. com.local.burrete10.sdf
   Content type: Structure-data molecular file
   MIME types registered: chemical/x-mdl-sdfile
   UTI is registered with the system

When macOS looks up sdf it finds com.mdli.sketchfile first and uses the appropriate QuickLook generator. The order in which entries appear in the database will vary from Mac to Mac depending on the order in which applications were installed. Finder’s Get Info command allows you to target files to a specific app for opening, but has no effect on app extensions providing QuickLook previews and Finder icon thumbnails.

The Burette developer Sergei Nikolenko has done a fabulous job in sorting this out and the latest update is pretty reliable. Now when you QuickLook at a file the icon changes to reflect the contents of the file, as shown below, where the top right icon has changed from a generic icon to the view of the file contents

This it is also visible when you use “Get Info”

Whilst QuickLook can be viewed by simply hitting the spacebar, using option-space opens in full screen, it can also be activated from the command-line

qlmanage -p <path to file>

The more options are available if the file is opened in the Burette app itself as shown below.

Right-click on the ligand reveals a dropdown menu with additional options.

Double-click on the ligand to bring up a close up view showing ligand interactions

If you open a 2D sdf file there is an option to convert to 3D

There can of course be multiple reasonable conformations but the 3D structure generated is a reasonable starting point.

Burette is a really nice application, it is clearly a work in progress and the developer is really responsive so please try it out and provide feedback.

Credit also goes to the open-source projects behind much of the 3D viewing: Mol* (https://molstar.org/) provides the interactive molecular visualisation, while XYZRender (https://github.com/aligfellow/xyzrender) powers the publication-quality rendering in the XYZR view.

If you have time please come along and cheer on all the walkers and if you are able to donate to the very worthy cause I’d be very grateful.

https://www.justgiving.com/page/christopher-swain-1

This CICAG Distillate includes articles covering a diversity of aspects of chemical information, computer applications, and AI in chemistry, including:

Introduction to your CICAG Committee

Cheminformatics: a Digital History – Part 8. Reflections from the Early Years of My Career Doing STUFF

Bridging the Digital-to-Clinical Gap: A Roadmap for Predictive Drug Discovery

Beyond Molecules and Reactions: Hypergraphs as a New Structure for Chemistry

CICAG Members’ Publications

Consolidated overview of other Chemical Information News

Plus event reports, press releases, news from relevant organisations and projects, proposed and planned future events, and a book review.

https://morphing.cloud/hypercard

FEATURES

• Run HyperCard stacks directly on your modern Mac. No emulator required!
• Browse the Internet Archive’s HyperCard collection and run stacks with one-click.
• Period-accurate typography.
• Sound, instruments, and MacinTalk speech synthesis.
• Cross-stack navigation.

ChemScribble looks like a well thought out chemical drawing package, whilst you can use a mouse it is clearly designed with pen/stylus input in mind. It is now available as a public beta (https://www.chemscribble.com).

ChemScribble is available for MacOS, Windows and Linux, For Mac users, ChemScribble works with an iPad in sidecar and an Apple Pencil. They are actively developing a web version of ChemScribble to make it even more accessible, and will continue to evaluate native iOS and Android applications as the project grows and user demand evolves.