title: Computational modeling reveals molecular details of epidermal growth factor binding.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Chemical Engineering, University of Delaware, Newark, DE, USA. mayawala@che.udel.edu
authors.forename: Kapil
authors.initials: K
authors.lastname: Mayawala
authors.forename: Dionisios G
authors.initials: DG
authors.lastname: Vlachos
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Edwards
mesh_terms: D003198:Computer Simulation; D004058:Diffusion; D019281:Dimerization; D004815:Epidermal Growth Factor / Q000737:chemistry* / Q000378:metabolism; D066246:ErbB Receptors / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D009010:Monte Carlo Method; D011485:Protein Binding
chemical_list: D004815:Epidermal Growth Factor; D066246:ErbB Receptors