The molecular basis of IGF-II/IGF2R recognition: A combined molecular dynamics simulation, free-energy calculation and computational alanine scanning study

Jingjing Guo, Xiaoting Wang, Huijun Sun, Huanxiang Liu, Xiaojun Yao

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20 引文 斯高帕斯(Scopus)

摘要

Insulin-like growth factor-II (IGF-II) is a key regulator of cell growth, survival, migration and differentiation, and is thus pivotal in many cancers. An individual with a high IGF-II level is at high risk of developing cancer, whereas IGF2R is implicated as being important in tumor suppression. Thus, uncovering the essence of the IGF-II/ IGF2R interaction is very important to understanding the origin of the tumor-suppressing effect of IGF2R. In this study, in order to investigate the interaction of the IGF-II/ IGF2R complex and to characterize the binding hot spots of this interaction, a 10 ns molecular dynamics simulation combined with MM-PBSA/MM-GBSA computations and computational alanine scanning was performed on the IGFII/ IGF2R complex. From the results of the free-energy decomposition and the computational alanine scanning calculation, we identified the key residues in the IGF-II/ IGF-2R interaction. The results from the calculation were consistent with reported experimental mutagenesis studies. The information on the interaction of IGF-II and IGF2R obtained is vital for understanding how the structure of IGF2R influences the function of IGF-II in growth and development. This study will also lead to new opportunities to develop molecular probes that can assist in diagnostic screening, and even novel approaches to controlling tumor development.

原文English
頁(從 - 到)1421-1430
頁數10
期刊Journal of Molecular Modeling
18
發行號4
DOIs
出版狀態Published - 4月 2012
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