Some incredibly exciting news from the world of protein engineering. A new paper in Nature introduces BindCraft, an open-source and automated pipeline that's poised to change de novo protein binder design forever.
For anyone who's ever worked with protein-protein interactions, you know how complex and challenging it can be to design binders from scratch. It's often a painstaking process with low success rates.
But BindCraft reports experimental success rates of 10-100%!!!
BindCraft uses the learned "knowledge" (weights) of AlphaFold2 to generate binders. This means it can predict and design high-affinity binders without the need for traditional high-throughput screening or experimental optimization.
This is huge, because they're moving towards a paradigm where computational design can directly yield effective binders, even against challenging targets and without pre-existing binding site information.
They've already successfully designed binders against a diverse range of tough targets, including Cell-surface receptors, Common allergens (like reducing IgE binding to birch allergen), de novo designed proteins, and Multi-domain nucleases like CRISPR-Cas9 (they can modulate its activity).
An incremental improvement this is not. Its a fundamental shift in how we can approach protein engineering. The potential for therapeutics, diagnostics, and biotechnology is absolutely enormous.
From The Nature Paper:
"Protein–protein interactions are at the core of all key biological processes. However, the complexity of the structural features that determine protein–protein interactions makes their design challenging.
Here we present BindCraft, an open-source and automated pipeline for de novo protein binder design with experimental success rates of 10–100%. BindCraft leverages the weights of AlphaFold2 (ref. 1) to generate binders with nanomolar affinity without the need for high-throughput screening or experimental optimization, even in the absence of known binding sites.
We successfully designed binders against a diverse set of challenging targets, including cell-surface receptors, common allergens, de novo designed proteins and multi-domain nucleases, such as CRISPR–Cas9.
We showcase the functional and therapeutic potential of designed binders by reducing IgE binding to birch allergen in patient-derived samples, modulating Cas9 gene editing activity and reducing the cytotoxicity of a foodborne bacterial enterotoxin.
Last, we use cell-surface-receptor-specific binders to redirect adeno-associated virus capsids for targeted gene delivery.
This work represents a significant advancement towards a ‘one design-one binder’ approach in computational design, with immense potential in therapeutics, diagnostics and biotechnology."