Prototype Scripts for Hydrogen Bonding in Complex Structures, Co-Crystal Prediction, and Void Analysis
We are making some exciting new scripts available to CSD-Materials and CSD-Enterprise licence holders in the 2025.3 release. These scripts, originally developed for the Crystal Form Consortium, can be used to analyse structures and predict interactions in new ways. They are prototypes, and are being more generally released to seek feedback and an understanding of their utility – we will use them to assess whether to add new features into our software in the future. Once we’ve assessed the utility of the scripts we will remove them and either add the feature into our roadmap or look at other potential features. Please do send us any feedback on these prototypes by emailing hello@ccdc.cam.ac.uk.
The new scripts are High Z Prime HBP, Interaction Analysis, and Void Network.
High Z Prime HBP
The functionality provided in this script enables the user to execute a hydrogen bond propensity (HBP) analysis on structures with variable numbers of molecules in the asymmetric unit (varied Z’) and comparison of polymorph families.
The script can be applied to a folder of structures, a structure file containing one or more structures, or a single structure in the Mercury window. The script outputs HBP results comparing polymorph families, including a single landscape plot representing the hydrogen bond networks for polymorphic structures with different numbers of molecules in the asymmetric unit, as well as tables/plots comparing individual contributing hydrogen bonds.
The script can also produce plots that are easier to interpret for structure(s) containing several molecules in the asymmetric unit, breaking down the hydrogen bonding by component so differences/similarities become clearer.
Interaction Analysis
By identifying the functional groups present in the structure in the Mercury window and leveraging the Cambridge Structural Database (CSD), the interaction analysis script can identify the molecules most likely to co-crystallize with your molecule of interest.
The script identifies functional groups which commonly interact, and from a library of molecular structures (such as a co-former library), highlights the molecules that contain complementary functional groups. By looking at every functional group and identifying the number of times a co-former exhibits one of the high likelihood interactions with those groups, an interaction analysis score is derived, to help rank potential co-formers. This analysis can also be used with a solvent library to find solvents that show high likelihood interactions with molecules of interest.
The script produces an HTML summary (which will appear in a browser window) that provides a ranked list of molecules from the library for multi-component analysis. A more detailed word document is also produced, with a breakdown of the likely groups to interact for each functional group in the target molecule, ranking for both multi-component and single-component analysis, and some information on the methodology used.
Void Network
The Void Network tool goes beyond the functionality found in the Display → Voids tool and enables the user to analyse the structure in the Mercury window in more detail. The script:
- Measures individual void volume
- Classifies pockets and channels
- Identifies nearby atoms (hydrogen bond donors and acceptors)
- Groups symmetry equivalent pockets
The script produces HTML output enabling visualisation of the voids in the unit cell with an interactive image.
How to Run the Scripts
The scripts are available in the 2025.3 version of Mercury. Before running a script, you may first need to open the structure that you are interested in analysing, either from a database or from a file. To start a script, open the CSD Python API menu. You should see the scripts under Prototypes.
Some of the scripts can take some time – you may wish to change the default timeout by going to CSD Python API → Options… and editing the “Time out for script” option – for example you could change this to 00:10:00 for a ten minute time out.
For the High Z Prime HBP script, after launching, you will get some options including which structure(s) to analyse and an option to see the advanced settings. If you check the advanced settings dialog you can adjust some of the settings of the HBP calculation. This script will run for some time and may result in a timeout message. If it does give a time out message, the script will continue to run with results saved into the output folder hyperlinked at the top of the window (any errors will be captured in the warning_statements.txt file).
For the Interaction Analysis script, you will need to load the target structure into the Mercury viewing window first. Once you run the script, you will get an options dialog to allow you to select a different co-former library (default is the CSD co-former library) – to do this, check the box for “Select a different coformer library”. When prompted, select the folder of structures (as .mol2 files) that you wish to use as your co-former library. If you check the Advanced Setting dialogue, you can adjust some of the settings in Interaction Analysis.
For the Void Network script, you will need to load the target structure into the Mercury viewing window first. Once you run the script, you will get an options dialog allowing you to set the probe radius, the grid spacing and an atom inclusion threshold. Clicking “Continue” will produce a short report in HTML format, which will appear in a browser window.
Next Steps
Contact us here to discuss further and/or request a demo with one of our scientists.