Holehouse and Sukenik labs present GOOSE framework for IDR design
This digest was compiled by AI from multiple sources — links to the originals are below.
An international research team led by the Holehouse and Sukenik labs has unveiled GOOSE, a computational framework that enables the rational design of intrinsically disordered proteins (IDRs). The framework, described in a Nature paper, allowed the team to design and test thousands of IDR sequences, revealing distinct sequence-to-function relationships. The designed IDRs demonstrated the ability to respond to cellular stress, self-assemble into scaffolds, and protect cells from desiccation.
The GOOSE Framework
GOOSE (Generate disOrdered prOteins Specifying propErties) is an open-source computational platform for designing intrinsically disordered protein regions. It allows researchers to specify desired sequence properties and generate IDRs that meet those criteria. The framework's high throughput enabled testing of thousands of sequences in cellular environments. The work, published in Nature, was led by the Holehouse lab and Sukenik lab, with data and code deposited on GitHub and Zenodo.
Functional Design Applications
Using GOOSE, the team designed IDRs that change their structural ensemble in response to cell volume decrease. They also created scaffold IDRs capable of self-assembling and recruiting specific client molecules. Additionally, novel IDRs were designed that protected cells from desiccation, a stress condition that is lethal to most organisms. These results demonstrate the power of rational design to probe sequence-function relationships in disordered proteins.
Data and Code Sharing
All data and analysis scripts have been deposited on GitHub and Zenodo, with raw sequencing data available via Zenodo. The GOOSE codebase is fully open source and accessible on GitHub, with documentation provided on Read the Docs. Interactive notebooks allow researchers to generate sequences and design IDR-IDR interactions through Google Colab. This transparency is intended to accelerate adoption by the molecular biology community.
What's Next
The team plans to extend GOOSE to incorporate additional sequence features and biological contexts. It remains unclear how these designed IDRs will perform in more complex multicellular organisms or therapeutic applications.
1 source
Holehouse and Sukenik labs present GOOSE framework for IDR design
