Figure 2
Molecular modeling of the 3D structure of VEGF165 dimer and energy contribution analysis. Two distinct conformations of the VEGF165 dimer in complex with VEGFR-2 refined by MD simulations are obtained: “twisted” (a) and “straight” (b). VEGF165 models (twisted and straight) and VEGFR-2 are depicted in molecular surface and cartoon representation, respectively. The RBD is shown in gray (dark and light representing each monomer), the HBD in blue (dark and light representing each monomer) and VEGFR-2 in yellow. Charged residues at the HBD of VEGF165 interacting with VEGFR-2 are highlighted in pale (dark and light for each monomer) and numbered (VEGF165 monomers are distinguished by a comma). Residue R165, which is essential for NRP-1 recognition, is not interacting in the “straight” model and is shown in green (dark and light for each monomer). Close-up of the MD refined complex of VEGFR-2 with VEGF165-HBD twisted (c) and straight (d) models with relevant interacting residues in sticks, colored by atom type and labeled. The no interacting residue R165 in the VEGF165 straight model is labeled in italic. Per-residue energy analysis (calculated with MM-GBSA from MD simulations) of most contributing residues of VEGF165-HBD twisted (e) and straight (f) models in binding to VEGFR-2.
