Heat flow random walks in biomolecular systems using symbolic transfer entropy and graph theory.

This study combines the information- and graph-theoretic measures to investigate the cluster modulation of the amino acid residues and nucleotides at complex biomolecular interfaces. The symbolic transfer entropy is used as an information-theoretic measure. I also used graph theory to obtain information and heat flow weighted digraph models used to study the topology of information and heat flow paths at complex biomolecular interfaces. I introduce the graph-theoretic measures, such as the influence score and betweenness centrality, to identify the most influential amino acid and nucleotide sequences as sources of the information and absorb centers of the structure's heat flow. PageRank-like random walks algorithm is used to analyze the network of amino acid and nucleotide sequences at the protein-RNA interface combined with weighted digraph models. The cluster analysis using graph-theoretic measures revealed the modular molecular structure and the mechanism of the binding interface. In this study, the first benchmark system is an intuitive directed information flow network used to test the algorithms, and the second benchmark is a protein-RNA complex system. The approach was able to identify the most influential amino acid residues and nucleotides. Furthermore, the statistical cluster analysis using graph-theoretic measures revealed the modular molecular structure and the binding mechanism at the interface.