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

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1421-1430
Number of pages10
JournalJournal of Molecular Modeling
Volume18
Issue number4
DOIs
Publication statusPublished - Apr 2012
Externally publishedYes

Keywords

  • Computational alanine scanning
  • IGF-II/IGF2R interaction
  • Molecular dynamics simulation
  • Molecular mechanics generalized born surface area (MM-GBSA)
  • Protein-protein interaction

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