Frontier Highlight: Arne Schneuing’s DiffSBDD Revolutionizes Drug Design
Frontier Highlight: Christopher Frank’s Af2Cycler Breakthrough in Large Protein Design
Christopher Frank and his collaborators have introduced the af2cycler, a cutting-edge design pipeline that refines large protein backbones with remarkable precision. Leveraging AlphaFold2 (AF2) alongside ProteinMPNN, this innovation enhances structural integrity and designability of proteins up to 1,500 amino acids, breaking barriers in de novo protein design.
Key Features of Af2Cycler:
Refined Large Proteins: Initial designs by Chroma are improved through AF2’s denoising capabilities, yielding backbones with higher structural accuracy.
Iterative Optimization: By cycling sequences and structures through AF2 and ProteinMPNN, af2cycler achieves convergence on high-quality designs with minimal deviations from the original blueprint.
High Experimental Success: Laboratory tests on 1,000-AA proteins, shaped as letters of the Latin alphabet, demonstrated alignment with computational predictions and successful structural validation through TEM imaging.
Scalable Applications: Af2cycler proves its potential for proteins beyond 1,500 amino acids, hinting at applications in multi-state backbone optimization and complex protein assemblies.
Impact on Protein Design: This breakthrough provides a robust framework for creating large proteins tailored to precise structural and functional demands. With af2cycler, the challenges of designing stable, complex protein backbones are significantly reduced, paving the way for transformative advancements in synthetic biology and therapeutic protein engineering.
Explore the full details in the preprint: “Alphafold2 refinement improves designability of large de novo proteins” by Christopher Frank et al., available on bioRxiv: https://doi.org/10.1101/2024.11.21.624687.
