Molecular dynamics-based model of VEGF-A and its heparin interactions

Considering both small and large scale motions of vascular endothelial growth factor (VEGF) is crucial for reliably predicting its binding affinities to DNA aptamers

“…In fact, the multiple pose binding nature between HBD of VEGF and its ligand driven by electrostatic interactions has also been reported previously. 12 In addition, we note that binding affinities have been reasonably reproduced by docking scores without actual free energy calculations. 25,26 Thus, it is clear that we have to somehow include the exible nature of the protein for our computations.…”

“…Such a multiple pose binding nature of HBD has been also reported previously against heparin ligand. 12 Although we closely reproduced the binding affinity order between VEGF 165 and DNA aptamers based on docking scores, there are still two issues to be claried in order to substantiate the validity of our docking scheme. One is the validity of considering only lowest frequency normal mode in generating large-scale motions of VEGF 165 , and the other is the validity of examining only one initial structure (Structure 11 in Fig.…”

“…Therefore, despite the potential as a promising drug target against AMD, no docking study considering the whole structure of VEGF 165 has been carried out, except one recent study that examined the interaction between VEGF 165 and heparin. 12 Even in that study, the exibility of VEGF 165 was not taken into account during docking.…”

Glycosaminoglycan–Protein Interactions: The First Draft of the Glycosaminoglycan Interactome

“…Docking combined with molecular dynamics simulations has been used to investigate GAG–protein complexes 63 such as those formed with growth factors (e.g., vascular endothelial growth factor-A-HP), 64 with ECM proteins such as those formed by procollagen C-proteinase-enhancer-1 with several GAGs 65 or by ECM bioactive fragments such as the propeptide of lysyl oxidase with a HP hexasaccharide. 66 A benchmarking study, including eight docking softwares for 28 GAG–protein complexes, has concluded that the combination of several molecular docking programs and other modeling approaches such as molecular dynamic improves the prediction and evaluation of GAG-binding poses.…”

Heparin and heparan sulfate proteoglycans promote HIV-1 p17 matrix protein oligomerization: computational, biochemical and biological implications

“…For what concerns bioinformatics, the docking of protein to heparin (used as a structural analog of HSPGs) and molecular dynamics (MDs) have been limited only to short (di-, tetra- or hexa-) oligosaccharides, mainly due to heparin conformational flexibility and high charge density, the weak surface complementarity of heparin/protein interactions, the absence of well-defined binding pockets, the difficulty to define the impact of solvation/desolvation, the large electrostatic interactions involved and the large number of torsional angles between glycosidic bonds 22,23 . Only in selected cases, 14-mer heparin oligosaccharides were used with molecular docking to study FGF 24 , VEGF 25 and CXCL8 26 dimerization. Relevant to this point, longer heparin or heparan sulfate (HS) chains are found in nature that are responsible for cytokine oligomerization.…”