5^th Global Chemistry Congress

The identification of computational tools to analyze the relationship between protein function and structure is a hot research field since 1960s. Despite the advancement of both experimental methods and computational tools,it is still lacking a benchmark methodology identifying clearly and without biases the relationship between structural properties and recognized protein functions. Inspired by the classical theory of Debye-Huckel, we propose a new interpretation of protein contact networks so to define the structural formula of proteins as the network of non-covalent intramolecular bonds. In this way, the peptide bonds would embody the role of nuclear bonds in organic molecules, too strong to determine the adaptation of the molecule to environment. On the other hand, non-covalent intramolecular bonds, which rearrange during protein adaptation of proteins to environment stimuli, represent the right level of analysis to define protein functionality. As for the organic molecules, through chemical graph theory, it is possible to identify key topological parameters fitting with protein properties (protein stability, allostery). The predictive potentiality of the methodology is stunning: once the structural data are available (from X-ray crystallography on NMR), the protein contact network formalism may allow quantifying protein functionality (such as allosteric sites in enzymes or hot spot residues in protein-protein interactions).

 

References:

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