Model for the complex between the insulin-like growth factor I and its receptor: towards designing antagonists for the IGF-1 receptor.

The type-1 insulin-like growth factor receptor (IGF-1R) is the cognate tyrosine kinase receptor for the insulin-like growth factor IGF-I and is expressed widely in many foetal and postnatal tissue cells. IGF-1R is overexpressed in a number of human tumour types and is a valid target for anti-cancer therapeutic efforts. Designing antagonists for IGF-1R would be greatly facilitated by the availability of structural information on the complex between IGF-I and IGF-1R. In the present work we model the three-dimensional structure of the complex between IGF-I and the first three domains of IGF-1R using a macromolecular docking method guided by selected experimental data. Interface metrics indicative of the binding affinity and reliability of the model are computed and compared with other biomolecular complexes. This model is consistent with experimental chimerical and mutagenesis data, provides a structural basis for understanding the primary interaction of IGF-I with its receptor and facilitates design of antagonist ligands.