title: Dynamical behavior of the vascular endothelial growth factor: biological implications.
abstract: The vascular endothelial growth factor (VEGF) seems to be the most important regulator of physiological and pathological angiogenesis, being, for this reason, a favorite target for therapies against angiogenesis-related diseases. VEGF is a homodimer in which the monomers are formed by beta-strands interconnected on the poles by three loops. A recent work showed that an intimate relationship between loops-1 and -3 is required for high affinity binding to the receptors (Kiba et al., J Biol Chem 2003;278:13453-13461). In this work, we report the results of a 10-ns molecular dynamics simulation of VEGF. We analyzed the dynamical behavior of the protein (using a dynamical cross-correlation map) and found that it is governed by a high degree of correlation between the motions of the loops. We also performed a principal component analysis and found an overall motion in which the opposite poles are projected against each other, just like the movement of the wings of a butterfly. From the biological point of view, it is likely that this motion would facilitate receptor binding since VEGF must enter a restricted cavity formed by the two subunits of the receptor.
authors.affiliation: Physical Organic Chemistry Group, Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio de Janeiro, Cidade Universitária, 21949-900 Rio de Janeiro, RJ, Brazil. bruno@iq.ufrj.br
authors.forename: Bruno A C
authors.initials: BA
authors.lastname: Horta
authors.forename: José J V
authors.initials: JJ
authors.lastname: Cirino
authors.forename: Ricardo B
authors.initials: RB
authors.lastname: de Alencastro
mesh_terms: D003198:Computer Simulation; D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D025341:Principal Component Analysis; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013816:Thermodynamics; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry* / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A