Centrality in protein structure networks and molecular dynamics

Abstract

Tridimensional protein structures can be analyzed as graphs (Protein Structure Networks). On this analysis, the protein amino acid residues are the vertex of the network and both covalent and non-covalent interactions between residues are the edges. Therefore, this approach allows a global analysis of thousands of interactions responsible for keeping the structure of a protein, determining its function and properties. The analysis of protein structures as graphs allows the calculation of measurements called centrality, which relates to the relevance of an amino acid residue amongst the assembly of interactions of the protein structure, therefore, it is possible to estimate the importance of the amino acid residues for the protein properties. Residues involved in allosteric signaling, catalytic activity and thermostability were identified through this approach. Usually, the Protein Structure Networks are built from contact maps, conceived based on crystallographic structures. However, in solution the protein structure is dynamic because of the thermic energy and collision with other molecules. Ergo, changes on the noncovalent bonds between amino acid residues are expected and consequently changing the Structure Network in function of time. Therefore, the analysis of protein molecular dynamics by representation in networks may reveal residues or sets of residues that are transiently relevant for protein function. Therefore, the purpose of this project is to simulate the molecular dynamics of a protein (Sfbetagli, 5CG0), followed by the analysis of residue centralities and its hypothetical correlation. In conclusion, through this unprecedented approach, we can deepen our knowledge regarding the relationship between structure and function in proteins. (AU)