Unifying structural descriptors for biological and bioinspired nanoscale complexes

Biomimetic nanoparticles are known to serve as nanoscale adjuvants, enzyme mimics and amyloid fibrillation inhibitors. Their further development requires better understanding of their interactions with proteins. The abundant knowledge about protein–protein interactions can serve as a guide for designing protein–nanoparticle assemblies, but the chemical and biological inputs used in computational packages for protein–protein interactions are not applicable to inorganic nanoparticles. Analysing chemical, geometrical and graph-theoretical descriptors for protein complexes, we found that geometrical and graph-theoretical descriptors are uniformly applicable to biological and inorganic nanostructures and can predict interaction sites in protein pairs with accuracy >80% and classification probability ~90%. We extended the machine-learning algorithms trained on protein–protein interactions to inorganic nanoparticles and found a nearly exact match between experimental and predicted interaction sites with proteins. These findings can be extended to other organic and inorganic nanoparticles to predict their assemblies with biomolecules and other chemical structures forming lock-and-key complexes. Unified structural descriptors of geometrical and graph-theoretical features are developed, allowing knowledge about protein lock-and-key complexes to be utilized to predict the formation of and interaction sites in protein–nanoparticle pairs.