gapTrick—structural characterization of protein–protein interactions using AlphaFold
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Motivation
The structural characterization of protein–protein interactions is a key step in understanding the functions of living cells. Here, I show that AlphaFold3 often fails to predict protein complexes that are either weak or dependent on the presence of a cofactor that is not included in a prediction.
Results
To address this problem, I developed gapTrick, an AlphaFold2-based approach that uses multimeric templates to improve prediction reliability. I demonstrate that gapTrick improves predictions of weak and incomplete complexes based on low-accuracy templates, such as individual protein models that have been rigid-body fitted into cryo-EM reconstructions. I also show that gapTrick identifies residue–residue interactions with high precision. These interaction predictions are a very strong indicator of model correctness. The approach can aid in the interpretation of challenging experimental structures and the computational identification of protein–protein interactions.
Availability and implementation
The gapTrick source code is available at https://github.com/gchojnowski/gapTrick and requires only a standard AlphaFold2 installation to run. The repository also provides a Colab notebook that can be used to run gapTrick without installing it on the user’s computer.
