Journal of Molecular Modeling

, Volume 15, Issue 11, pp 1349–1370 | Cite as

A graph theoretical approach for assessing bio-macromolecular complex structural stability

  • Carlos Adriel Del Carpio
  • Mihai Iulian Florea
  • Ai Suzuki
  • Hideyuki Tsuboi
  • Nozomu Hatakeyama
  • Akira Endou
  • Hiromitsu Takaba
  • Eiichiro Ichiishi
  • Akira Miyamoto
Original Paper
First Online:
Received:
Accepted:

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.

Keywords

Protein–protein interaction Complex structural rigidity Biomolecular docking Scoring function 
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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Carlos Adriel Del Carpio
    • 1
  • Mihai Iulian Florea
    • 2
  • Ai Suzuki
    • 3
  • Hideyuki Tsuboi
    • 1
  • Nozomu Hatakeyama
    • 1
  • Akira Endou
    • 1
  • Hiromitsu Takaba
    • 1
  • Eiichiro Ichiishi
    • 4
    • 5
  • Akira Miyamoto
    • 1
    • 3
  1. 1.Department of Applied Chemistry, Graduate School of EngineeringTohoku UniversityAoba-kuJapan
  2. 2.Department of Electrical, Information and Physics Engineering, School of EngineeringTohoku UniversityAoba-kuJapan
  3. 3.New Industry Creation Hatchery Center (NICHe)Tohoku UniversityAoba-kuJapan
  4. 4.School of Materials ScienceJapan Advanced Institute of Science and TechnologyNomi-cityJapan
  5. 5.Graduate School of MedicineTohoku UniversityAoba-kuJapan

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