title: A graph theoretical approach for assessing bio-macromolecular complex structural stability.
abstract: Fast and proper assessment of bio macro-molecular complex structural rigidity as a measure of structural stability can be useful in systematic studies to predict molecular function, and can also enable the design of rapid scoring functions to rank automatically generated bio-molecular complexes. Based on the graph theoretical approach of Jacobs et al. [Jacobs DJ, Rader AJ, Kuhn LA, Thorpe MF (2001) Protein flexibility predictions using graph theory. Proteins: Struct Funct Genet 44:150-165] for expressing molecular flexibility, we propose a new scheme to analyze the structural stability of bio-molecular complexes. This analysis is performed in terms of the identification in interacting subunits of clusters of flappy amino acids (those constituting regions of potential internal motion) that undergo an increase in rigidity at complex formation. Gains in structural rigidity of the interacting subunits upon bio-molecular complex formation can be evaluated by expansion of the network of intra-molecular inter-atomic interactions to include inter-molecular inter-atomic interaction terms. We propose two indices for quantifying this change: one local, which can express localized (at the amino acid level) structural rigidity, the other global to express overall structural stability for the complex. The new system is validated with a series of protein complex structures reported in the protein data bank. Finally, the indices are used as scoring coefficients to rank automatically generated protein complex decoys.
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Tohoku University, Aoba-ku, Sendai, Japan. carlos@aki.che.tohoku.ac.jp
authors.forename: Carlos Adriel
authors.initials: CA
authors.lastname: Del Carpio
authors.forename: Mihai
authors.initials: M
authors.lastname: Iulian Florea
authors.forename: Ai
authors.initials: A
authors.lastname: Suzuki
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Tsuboi
authors.forename: Nozomu
authors.initials: N
authors.lastname: Hatakeyama
authors.forename: Akira
authors.initials: A
authors.lastname: Endou
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Takaba
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Ichiishi
authors.forename: Akira
authors.initials: A
authors.lastname: Miyamoto
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry; D030562:Databases, Protein; D016333:HIV Protease / Q000737:chemistry; D006860:Hydrogen Bonding; D046911:Macromolecular Substances / Q000737:chemistry*; D008958:Models, Molecular; D018583:Pliability; D055550:Protein Stability; D017433:Protein Structure, Secondary; D015203:Reproducibility of Results; D057057:Serine Proteases / Q000737:chemistry
chemical_list: D002352:Carrier Proteins; D046911:Macromolecular Substances; D057057:Serine Proteases; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1