Investigation of alanine mutations affecting insulin-like growth factor (IGF) I binding to IGF binding proteins

Binding properties of wild type (WT) and six single amino acid substituted variants (E3A, E9A, D12A, D20A, F23A, and E58A) of insulin-like growth factor I (IGF-I) were analyzed with respect to their binding details to IGF binding proteins (IGFBPs) by molecular dynamics (MD) simulations. The binding sites and binding interactions on IGF-I and IGFBPs are screened and compared with the static X-ray structure. Electrostatic interaction is the primary driving force of the interaction between IGF-I and IGFBPs. Mutation may cause the rearrangement of binding sites, however, the unfolding of protein induced by mutation is not obvious in this work. We also provide the detailed picture of binding factors. And the results show that, whether the unfolding of helix occurs or not, the Ala mutation will change the molecular atmosphere of the binding interface by the rearrangement of conformation, and further affects the binding residues and binding interactions.