Molecular mechanism of binding between a therapeutic RNA aptamer and its protein target VEGF: A molecular dynamics study.
Mahroof KalathingalYoung Min RheePublished in: Journal of computational chemistry (2023)
Macugen is a therapeutic RNA aptamer against vascular endothelial growth factor (VEGF)-165, the VEGF isoform primarily responsible for angiogenesis. It has been reported that Macugen inhibits angiogenesis by specifically binding to the heparin binding domain (HBD) of VEGF165. The mechanism of the molecular recognition between HBD and Macugen is investigated here using all-atom molecular dynamics simulations. We find that Macugen recognizes HBD by an induced-fit mechanism with major conformational changes in Macugen and almost no changes in the structure of HBD, whereas HBD recognizes Macugen by a conformational selection mechanism.
Keyphrases
- vascular endothelial growth factor
- molecular dynamics
- molecular dynamics simulations
- endothelial cells
- density functional theory
- high glucose
- gold nanoparticles
- molecular docking
- sensitive detection
- binding protein
- single molecule
- venous thromboembolism
- dna binding
- diabetic rats
- label free
- transcription factor
- high resolution
- atomic force microscopy
- amino acid