Shedding light on protein–ligand binding by graph theory: The topological nature of allostery

Allostery is a very important feature of proteins; we propose a mesoscopic approach to allosteric mechanisms elucidation, based on protein contact matrices. The application of graph theory methods to the characterization of the allosteric process and, more broadly, to obtain the conformational changes upon binding, reveals key features of the protein function. The proposed method highlights the leading role played by topological over geometrical changes in allosteric transitions. Topological invariants were able to discriminate between true allosteric motions and generic protein motions upon binding. [Display omitted] ► A graph theoretic method is proposed to analyze protein structure and function. ► The method is based on protein contact matrices. ► Application of the method shows the key role of topology in allosteric transitions.