Common Structural Cliques: a tool for protein structure and function analysis

Abstract

Proposed is a method for locating functionally relevant atoms in protein structures and a representation of spatial arrangements of these atoms allowing for a flexible description of active sites in proteins. The search method is based on comparison of local structure features of proteins that share a common biochemical function. The method does not depend on overall similarity of structures and sequences of compared proteins or on previous knowledge about functionally relevant residues. The compared protein structures are condensed to a graph representation, with atoms as nodes and distances as edge labels. Protein graphs are then compared to extract all possible Common Structural Cliques. These cliques are merged to create Structural Templates: graphs that describe structural analogies between compared proteins. Structures of serine endopeptidases were compared in pairs using the presented algorithm with different geometrical parameters. Additionally, a Structural Template was extracted from the structures of aminotransferases, two different proteins that catalyze the same type of chemical reaction. The results presented show that the method works efficiently even in the case of large protein systems and allows for extraction of common structural features from proteins catalyzing a particular chemical reaction, but that evolved from different ancestors by convergent evolution.

Comparing Graph Representations of Protein Structure for Mining Family-Specific Residue-Based Packing Motifs

“…Graphs have long been used to study organic molecules (Dehaspe et al, 1998;Borgelt and Berhold, 2002) and macromolecules such as nucleic acids (Klein, 1998;Wang et al, 1998) and proteins (Milik et al, 2003;Mitchell et al, 1990;Singh and Brutlag, 1997). Nongraph based approaches have been reported as well.…”

Graphical models of residue coupling in protein families

“…Such works boosted the discovery of coupled residues, which could previously have been identified only by painstaking in vitro approaches such as thermodynamic double mutant analysis [11]. The next step was to summarize information about correlated positions into pathways [15], motifs [1,20], and structural templates [20] in protein families. Today, projects undertake ambitious large-scale recombination [28] or site-directed and combinatorial mutagenesis studies [23] to identify entire building blocks of proteins important to preserve function.…”

Functional Neighbors: Inferring Relationships between Non-Homologous Protein Families Using Family-Specific Packing Motifs

“…-Graph matching methods have been developed to compare protein structures modeled as graphs, usually with clique detection techniques [2,21,30,36,12]. -Other methods include inductive programming language [32], fuzzy functional forms [10], computed protonation properties [22] and geometric depth potentials [39].…”