Computational modeling reveals molecular details of epidermal growth factor binding

被引:30
作者
Mayawala, K
Vlachos, DG [1 ]
Edwards, JS
机构
[1] Univ Delaware, Dept Chem Engn, Newark, DE 19716 USA
[2] Univ New Mexico, Canc Res & Treatment Ctr, Hlth Sci Ctr, Albuquerque, NM 87131 USA
关键词
D O I
10.1186/1471-2121-6-41
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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. Conclusion: 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.
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页数:11
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