275440 Insilico Multiscale Models for Identifying Driver Versus Passenger Mutations in Cancer Progression

Tuesday, October 30, 2012: 2:42 PM
Crawford East (Westin )
Ravi Radhakrishnan, Department of Bioengineering, University of Pennsylvania, Philadelphia, PA

We describe current advances in multiscale computational modeling and simulation approaches in our laboratory combining models in structural biology and those in systems biology. The overall aim is to build quantitative models of signaling networks while retaining the crucial elements of molecular specificity, which appear to be highly relevant to profiling and predictive modeling of clinical mutations in many transformed cell lines. We discuss current and emerging experimental and computational methods, particularly focusing on hybrid and multiscale methods, which we have developed, and highlight several applications in cell signaling with quantitative and predictive capabilities. The scope of such models range from delineating protein-protein interactions to describing clinical implications in the context of mutations in ErbB family receptors (EGFR, HER2, HER3, and HER4) in non-small-cell lung cancer, and ALK receptor in pediatric neuroblastoma.

Related References:

1.    Molecular Systems Biology of ErbB1 Signaling: Bridging the Gap through Multiscale Modeling and High-Performance Computing, Andrew Shih, Jeremy Purvis, R. Radhakrishnan, Molecular Biosystems (A Royal Society of Chemistry Journal), 4: 1151-1159, 2008.  Pubmed ID: 19396377

2.    Molecular Dynamics Analysis of Conserved Hydrophobic and Hydrophilic Bond Interaction Networks in ErbB Family Kinases, A. Shih, S. E. Telesco, S. H. Choi, M. A. Lemmon, R. Radhakrishnan, Biochemical Journal, 2011, 436(2), 241-251. Pubmed ID: 21426301.

3.    Analysis of Somatic Mutations in Cancer: Molecular Mechanisms of Activation in the ErbB family of Receptor Tyrosine Kinases, A. J. Shih, S. E. Telesco, R. Radhakrishnan, Cancers, 2011, 3(1), 1195-1231; doi:10.3390/cancers3011195. Pubmed ID: 21701703.

4.    A Multiscale Modeling Approach to Investigate Molecular Mechanisms of Pseudokinase Activation and Drug Resistance in the HER3/ErbB3 Receptor Tyrosine Kinase Signaling Network, S. E. Telesco, A. J. Shih, F. Jia, R. Radhakrishnan, Molecular Biosystems (RSC Journal), 2011, 7 (6), 2066 - 2080. DOI: 10.1039/c0mb00345j. Pubmed ID: 21509365.

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See more of this Session: Multiscale Systems Biology
See more of this Group/Topical: Topical A: Systems Biology