Method for identification of rigid domains and hinge residues in proteins based on exhaustive enumeration

• Published in: Proteins, structure, function, and bioinformatics Vol. 83; no. 6; pp. 1054 - 1067
• Main Authors: Sim, Jaehyun, Sim, Jun, Park, Eunsung, Lee, Julian
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01-06-2015; Wiley Subscription Services, Inc
• Subjects: Algorithms; Computational Biology - methods; DAGR; elastic network model; exact; exhaustive enumeration; graph theory; hinge; maximal clique; Molecular Dynamics Simulation; normal mode analysis; protein structure; Protein Structure, Tertiary; Proteins - chemistry; rigid domain; Sequence Analysis, Protein - methods; Software; protein structure; hinge; normal mode analysis; graph theory; elastic network model; DAGR; exhaustive enumeration; exact; maximal clique; rigid domain
• ISSN: 0887-3585; 1097-0134
• DOI: 10.1002/prot.24799

ABSTRACT
Many proteins undergo large‐scale motions where relatively rigid domains move against each other. The identification of rigid domains, as well as the hinge residues important for their relative movements, is important for various applications including flexible docking simulations. In this work, we develop a method for protein rigid domain identification based on an exhaustive enumeration of maximal rigid domains, the rigid domains not fully contained within other domains. The computation is performed by mapping the problem to that of finding maximal cliques in a graph. A minimal set of rigid domains are then selected, which cover most of the protein with minimal overlap. In contrast to the results of existing methods that partition a protein into non‐overlapping domains using approximate algorithms, the rigid domains obtained from exact enumeration naturally contain overlapping regions, which correspond to the hinges of the inter‐domain bending motion. The performance of the algorithm is demonstrated on several proteins. Proteins 2015; 83:1054–1067. © 2015 Wiley Periodicals, Inc.