This BioGRID themed curation project on synthetic protein interactions aims to annotate de novo designed proteins that have been experimentally validated to interact with the intended target. With a specific emphasis on de novo proteins designed using recent machine learning-based methods - including RFdiffusion, FoldFlow-2 and BindCraft.

• Protein Binder - Protein binders are synthetic proteins that attach to other proteins, nucleic acids or small molecules with high specificity and affinity.
• Minibinder - Minibinders are small, engineered proteins designed to specifically bind to target molecules, such as proteins or receptors, small molecules or nucleic acids.
• Multivalent MiniBinder - Multivalent minibinders are engineered proteins that contains multiple binding sites, allowing simultaneous binding to multiple target molecules. This multivalency enhances the binding strength and specificity. Multivalent minibinders are often composed of multiple minibinders with linking sequences between them.
• Monobody - Monobodies are a type of synthetic binding protein engineered from the fibronectin type III (FN3) domain, which is structurally similar to an antibody's variable domain but lacks disulfide bonds. Monobodies are designed to bind specific target molecules, much like antibodies, but they have unique advantages in stability and ease of production.
• Nanobody - Nanobodies are small, single-domain antibody fragments with the antigen-binding ability of a conventional antibody but significantly smaller size.
• Adnectin - Adnectins are a type of monobody (based on the fibronectin type III domain (FN3) of human fibronectin) used for therapeutic purposes.
• Single-chain variable fragments (scFvs) - Single-chain variable fragments (scFvs) are a type of antibody fragment in which the variable regions of the heavy (VH) and light (VL) chains of an antibody are linked together by a short peptide linker. This creates a single, monovalent binding site.
• Designed ankyrin repeat protein (DARPin) - DARPins are synthetic binding proteins engineered to mimic the structure and function of natural ankyrin repeat proteins.
• D-peptide analogue - D-peptide analogues are small protein-like chains designed to mimic the structure and function of natural peptides. Unlike regular peptides that are composed of L-amino acids, D-peptides are made up of D-amino acids.
• Neoleukin - Neoleukins are synthetic proteins designed to interact with the same receptors that interleukins do.
• Ubiquibody (uAb) - Ubiquibodies (uAbs) are synthetic E3 Ligases designed such that their target binding domains are replaced by an engineered peptide or protein that binds a natural protein of interest.
• EndoTag - EndoTags are synthetic proteins designed to trigger the endocytosis (internalization) of specific cell-surface receptors, often resulting in subsequent delivery to the lysosome and degradation.
• Cyclic Peptide - Cyclic peptides are peptide sequences that have been engineered to form a closed ring structure which enhances their structural stability, resistance to enzymatic degradation, target binding affinity, and can reduce off-target toxicity compared to linear peptides.