Attractor structures of signaling networks: Consequences of different conformational barcode dynamics and their relations to network-based drug design

Kristõf Z. Szalay, Ruth Nussinov, P. Csermely

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Conformational barcodes tag functional sites of proteins and are decoded by interacting molecules transmitting the incoming signal. Conformational barcodes are modified by all co-occurring allosteric events induced by post-translational modifications, pathogen, drug binding, etc. We argue that fuzziness (plasticity) of conformational barcodes may be increased by disordered protein structures, by integrative plasticity of multi-phosphorylation events, by increased intracellular water content (decreased molecular crowding) and by increased action of molecular chaperones. This leads to increased plasticity of signaling and cellular networks. Increased plasticity is both substantiated by and inducing an increased noise level. Using the versatile network dynamics tool, Turbine (www.turbine.linkgroup.hu), here we show that the 10 % noise level expected in cellular systems shifts a cancer-related signaling network of human cells from its proliferative attractors to its largest, apoptotic attractor representing their health-preserving response in the carcinogen containing and tumor suppressor deficient environment modeled in our study. Thus, fuzzy conformational barcodes may not only make the cellular system more plastic, and therefore more adaptable, but may also stabilize the complex system allowing better access to its largest attractor.

Original languageEnglish
Pages (from-to)463-468
Number of pages6
JournalMolecular Informatics
Volume33
Issue number6-7
DOIs
Publication statusPublished - 2014

Fingerprint

Drug Design
Plasticity
Noise
Crowding
Molecular Chaperones
Post Translational Protein Processing
Pharmaceutical Preparations
Carcinogens
Plastics
Neoplasms
Proteins
Phosphorylation
Water
Health
Pathogens
Water content
Large scale systems
Tumors
Turbines
Cells

Keywords

  • Adaptation strategies
  • Attractors
  • Conformational barcodes
  • Drug design strategies
  • Fuzzy systems
  • Molecular memory
  • Network dynamics
  • Network plasticity
  • Network rigidity

ASJC Scopus subject areas

  • Organic Chemistry
  • Computer Science Applications
  • Drug Discovery
  • Molecular Medicine
  • Structural Biology

Cite this

Attractor structures of signaling networks : Consequences of different conformational barcode dynamics and their relations to network-based drug design. / Szalay, Kristõf Z.; Nussinov, Ruth; Csermely, P.

In: Molecular Informatics, Vol. 33, No. 6-7, 2014, p. 463-468.

Research output: Contribution to journalArticle

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