Computational modeling reveals molecular details of epidermal growth factor binding
1 Department of Chemical Engineering, University of Delaware, Newark, DE, USA
2 Molecular Genetics and Microbiology, Cancer Research and Treatment Center, University of New Mexico Health Sciences Center, and Chemical and Nuclear Engineering, University of New Mexico, Albuquerque, NM, USA
BMC Cell Biology 2005, 6:41 doi:10.1186/1471-2121-6-41Published: 30 November 2005
The ErbB family of receptors are dysregulated in a number of cancers, and the signaling pathway of this receptor family is a critical target for several anti-cancer drugs. Therefore a detailed understanding of the mechanisms of receptor activation is critical. However, despite a plethora of biochemical studies and recent single particle tracking experiments, the early molecular mechanisms involving epidermal growth factor (EGF) binding and EGF receptor (EGFR) dimerization are not as well understood. Herein, we describe a spatially distributed Monte Carlo based simulation framework to enable the simulation of in vivo receptor diffusion and dimerization.
Our simulation results are in agreement with the data from single particle tracking and biochemical experiments on EGFR. Furthermore, the simulations reveal that the sequence of receptor-receptor and ligand-receptor reaction events depends on the ligand concentration, receptor density and receptor mobility.
Our computer simulations reveal the mechanism of EGF binding on EGFR. Overall, we show that spatial simulation of receptor dynamics can be used to gain a mechanistic understanding of receptor activation which may in turn enable improved cancer treatments in the future.