The TopoBuilder is a framework for template free de novo protein design and is specifically useful for the construction of protein scaffolds around functional structural motifs of interest. It has been fully re-implemented in a modular, seamless fashion with many new features and utilites that make it easy to modify and customize.
This repository contains the TopoBuilder framework as described in: Zander Harteveld, Jaume Bonet, Stéphane Rosset, Che Yang, Fabian Sesterhenn, and Bruno E. Correia. A hierarchical framework for layered de novo protein design. (2022)
The easiest way to install the TopoBuilder is via through pip:
pip install topobuilderTo complete a TopoBuilder pipeline you will need:
- Python (3.7)
- PSIPRED (4.0): Secondary structure prediction from a protein sequence.
- Rosetta (3.9): Used for fragment assembly and sequence design of the final model.
- MASTER (1.6): Needed for fast protein structure searches for calculating per secondary structure element (SSE) corrections and loop searches.
The statistics plugin contains mutliple options that will require additional dependencies (optional):
- MolProbity: To calculate the MolProbity score.
- trRosetta: To predict a possible model directly from the designed sequence (with all dependencies installed).
- TMalign: To calculate a TMscore between the trRosetta model and the TopoBuilder model.
The code lives within the [topobuilder](topobuilder/) directory. We will briefly go through the most important ones:
- core: Initialization and configurations.
- case: Creates and handles the internal case object.
- form: Fabric to create ideal structural SSE assemblies.
- utils: Utility functions shared across multiple plugins.
- base_plugins: Various plugins to do different manipulations on the case object.
Please see the documentation for further explanation of all entry-points, plugins (and how to create your own custom plugin) and utilities available. Additional, we explain how to setup a pipeline and showcase different examples here.