Physical nature of intermolecular interactions inside Sir2 homolog active site: molecular dynamics and ab initio study.
Journal of molecular modeling
confidence
Key findings
Computational study of intermolecular interactions in Sir2 homolog (Hst2) active site with ADP-HPD; no clinical or biological endpoints reported.
View source on PubMed (PMID 27154340) ↗
- Sample size
- N/A
- Population
- In silico molecular modeling (yeast Hst2 Sir2 homolog)
- Dosing
- N/A
- Duration
- N/A
- Route
- N/A
- Blinding
- not_reported
- Controls
- none
- Drug class
- coenzyme
Full abstract
In the present study, we analyze the interactions of NAD+-dependent deacetylase (Sir2 homolog yeast Hst2) with carba-nicotinamide-adenine-dinucleotide (ADP-HPD). For the Sir2 homolog, a yeast Hst2 docking procedure was applied. The structure of the protein-ADP-HPD complex obtained during the docking procedure was used as a starting point for molecular dynamics simulation. The intermolecular interaction energy partitioning was performed for protein-ADP-HPD complex resulting from molecular dynamics simulation. The analysis was performed for ADP-HPD and 15 amino acids forming a deacetylase binding pocket. Although the results indicate that the first-order electrostatic interaction energy is substantial, the presence of multiple hydrogen bonds in investigated complexes can lead to significant value of induction component.