Journal
MOLECULAR INFORMATICS
Volume 33, Issue 6-7, Pages 463-468Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/minf.201400029
Keywords
Adaptation strategies; Attractors; Conformational barcodes; Drug design strategies; Fuzzy systems; Molecular memory; Network dynamics; Network plasticity; Network rigidity
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Funding
- National Cancer Institute, National Institutes of Health [HHSN261200800001E]
- Hungarian National Science Foundation [OTKA K83314]
- NIH, National Cancer Institute, Center for Cancer Research
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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.
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