Universal architectural concepts underlying protein folding patterns

Abstract

What is the architectural 'basis set' of the observed universe of protein structures? Using information-theoretic inference, we answer this question with a comprehensive dictionary of 1,493 substructural concepts. Each concept represents a topologically-conserved assembly of helices and strands that make contact. Any protein structure can be dissected into instances of concepts from this dictionary. We dissected the world-wide protein data bank and completely inventoried all concept instances. This yields an unprecedented source of biological insights. These include: correlations between concepts and catalytic activities or binding sites, useful for rational drug design; local amino-acid sequence-structure correlations, useful for ab initio structure prediction methods; and information supporting the recognition and exploration of evolutionary relationships, useful for structural studies. An interactive site, PROÇODIC, at http://lcb.infotech.monash.edu.au/prosodic (click) provides access to and navigation of the entire dictionary of concepts, and all associated information.