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De Novo Miniprotein Design

Miniproteins are a class of small, highly stable proteins (~75-100 AAs), shown to have good binding (nanomolar) and specificity against a diverse set of targets. De novo miniprotein design involves creating new protein binders from scratch to target specific molecules or surfaces.

Peptide Binder Design

Peptides offer advantages as therapeutic binders due to their small size, ease of synthesis, and ability to target difficult binding sites. Design approaches include both linear and macrocyclic peptides.

Antibody CDR Design

These protocols focus on engineering the variable regions of antibodies to improve binding affinity, specificity, and developability. Inverse folding methods such as IgDesign from Absci and AntiFold from OPIG start from structures of antibody–antigen complexes and redesign complementarity-determining regions (CDRs) for improved binding against the target. This process can be understood as more of an optimization task. Conversely, de novo antibody design approaches such as RFantibody, Germinal, BoltzGen, and mBER start from an antigen structure and generate CDR structures and sequences from scratch on a fixed framework. These methods are best suited for epitope-targeted binder discovery. All of these approaches except mBER are applicable to both scFvs and VHHs.

Small Molecule Binder Design

Designing protein binders for small molecules enables creation of biosensors, enzyme active sites, and therapeutic proteins that recognize specific ligands.

Motif / Interface Scaffolding

Interface scaffolding involves designing protein scaffolds to present functional motifs or binding interfaces in specific orientations.

Binder Optimization

Optimizing existing protein binders involves improving their binding affinity, specificity, and stability through targeted mutations and structural modifications.

Improving Stability

Improving protein stability involves modifying sequences and structures to enhance thermal stability, resistance to aggregation, and overall robustness. We’ve found stabilizing mutations recommended by ThermoMPNN to correlate well with experimental results.

Solubilizing Membrane Proteins

Engineering a target membrane protein to be soluble in solution without detergent, while keeping as much of the structural features intact as possible.