EnzyMM - The Enzyme Motif Miner

Identify catalytic sites in protein structures with the Enzyme Motif Miner!

Overview

EnzyMM is a Python tool to identify known patterns of catalytic residues in protein structures. We also provide a webserver where you can run EnzyMM on single queries here.

Catalytic sites, which define the function of proteins, are among the most conserved parts of enzyme structures. It makes sense therefore, that their similarities can be identified even if the rest of the protein has diverged throughout the course of evolutionary history. Similarly doing so immediately gives biological insight into possible functions. Proteins carry out a myriad of different functions. Yet constrained by the chemistry of life, given access to a toolkit of just 20 amino acids, often the same catalytic patters emerge. This means that by focusing on catalytic sites, functional convergence around similar mechanisms and structures can be detected. This makes EnzyMM fundamentally knowledge based and interpretable.

While proteins are commonly explored and compared using sequence based methods, these suffer various drawbacks. Principally it is not immediately apparent which part of the sequence is most important. Secondly, sequence diverges much faster than structure obscuring similarities as proteins mutate and evolve. Sequence rearrangements can completely break certain approaches.

With PyJess and EnzyMM we develop an extremely fast yet precise way to identify known catalytic patters without any of the drawbacks of sequence based methods. Thanks to very detail-oriented yet large scale curation efforts in the M-CSA and some clever engineering we can scan most protein structures against nearly 7000 catalytic arrangements in tenths of a second. Perfectly suited for exploring the expanding universe of predicted protein structures, we are excited to present EnzyMM!

For further information please refer to our scientific preprint of EnzyMM titled “Investigating Enzyme Function by Geometric Matching of Catalytic Motifs”

🔧 Setup

EnzyMM is available for all modern Python versions (3.8+).

Run pip install enzymm in a shell to download the latest release from PyPI, or have a look at the Installation page to find other ways to install EnzyMM.

Alternatively, we provide both Docker and Apptainer Images 🖼️.

📚 Library

Contents:

• User Guide
  • Installation
  • Command Line Interface
  • Understanding Templates
  • EnzyMM Output
  • Contribution Guide
  • Changelog
  • Copyright Notice
• API Reference
  • Input
  • Templates
  • Matching
  • M-CSA
  • Output

🔎 Related Projects

EnzyMM draws on a library of catalytic templates derived by Ioannis Riziotis from the Mechanism and Catalytic Site Atlas which is developed at the Thornton Group and maintained by Antonio Ribeiro.

EnzyMM utilizes PyJess, a Cython wrapper of JESS, for finding matches between templates and query structures. PyJess was developed by Martin Larralde. Please have a look at PyJess!

🔖 Citations

EnzyMM is academic software but relies on many previous approaches.

We kindly ask you to cite both:

• EnzyMM, for instance as:

  • Hackett RE et al. (2026), Investigating Enzyme Function by Geometric Matching of Catalytic Motifs [Preprint], BioRxiv, DOI:10.64898/2026.02.10.705182

• Mechanism and Catalytic Site Atlas as:

  • Ribeiro AJM et al. (2017), Nucleic Acids Res, 46, D618-D623. Mechanism and Catalytic Site Atlas (M-CSA): a database of enzyme reaction mechanisms and active sites. DOI:10.1093/nar/gkx1012. PMID:29106569.

⚖️ License

EnzyMM is provided under the MIT License. Both PyJess and the original JESS code are distributed under the MIT License as well.

Though conceived at the EMBL-EBI in Hinxton, UK in the Thornton Group, EnzyMM is now developed by Raymund Hackett and the Zeller Group at the Leiden University Medical Center in Leiden in the Netherlands with continuing support from the Thornton Group.