Geometry-based Computation of Symmetric Homo-oligomeric Protein Complexes

The need to engineer novel therapeutics and functional materials is driving the in-silico design of molecular complexes. This paper proposes a method to compute symmetric homo-oligomeric protein complexes when the structure of the replicated protein monomer is known and rigid. The relationship between the structure of a protein and its biological function brings the in-silico determination of protein structures associated with functional states to the forefront of computational biology. While protein complexes, arising from associations of protein monomers, are pervasive in every genome, determination of their structures remains challenging. Given the difficulty in computing structures of a protein monomer, computing arrangements of monomers in a complex is mainly limited to dimers. A growth in the number of protein complexes studied in wet labs is allowing classification of their structures. A recent database shows that most naturally-occurring protein complexes are symmetric homo-oligomers. The method presented here exploits this database to propose structures of symmetric homooligomers that can accommodate spatial replications of a given protein monomer. The method searches the database for documented structures of symmetric homo-oligomers where the replicated monomer has a geometrically-similar structure to that of the input protein monomer. The proposed method is a first step towards the in-silico design of novel protein complexes that upon further refinement and characterization can serve as molecular machines or fundamental units in therapeutics or functional materials.