title: Molecular docking and analysis of interactions between vascular endothelial growth factor (VEGF) and SPARC protein.
abstract: The extracellular module of SPARC/osteonectin binds to vascular endothelial growth factor (VEGF) and inhibits VEGF-stimulated proliferation of endothelial cells. In an attempt to identify the binding site for SPARC on VEGF, we hypothesized that this binding site could overlap at least partially the binding site of VEGF receptor 1 (VEGFR-1), as SPARC acts by preventing VEGF-induced phosphorylation of VEGFR-1. To this end, a docking simulation was carried out using a predictive docking tool to obtain modeled structures of the VEGF-SPARC complex. The predicted structure of VEGF-SPARC complex indicates that the extracellular domain of SPARC interacts with the VEGFR-1 binding site of VEGF, and is consistent with known biochemical data. Following molecular dynamics refinement, side-chain interactions at the protein interface were identified that were predicted to contribute substantially to the free energy of binding. These provide a detailed prediction of key amino acid side-chain interactions at the protein-protein interface. To validate the model further, the identified interactions will be used for designing mutagenesis studies to investigate their effect on binding activity. This model of the VEGF-SPARC complex should provide a basis for future studies aimed at identifying inhibitors of VEGF-induced angiogenesis.
authors.affiliation: Laboratory for Molecular Medicine, Office of Research, University of North Carolina at Greensboro, Greensboro, NC 27402-6170, USA.
authors.forename: Vasu
authors.initials: V
authors.lastname: Chandrasekaran
authors.forename: Jayakrishna
authors.initials: J
authors.lastname: Ambati
authors.forename: Balamurali K
authors.initials: BK
authors.lastname: Ambati
authors.forename: Ethan Will
authors.initials: EW
authors.lastname: Taylor
mesh_terms: D001665:Binding Sites; D008958:Models, Molecular; D015676:Osteonectin / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D015676:Osteonectin; D042461:Vascular Endothelial Growth Factor A