Molecular mechanics calculation of geometries of NAD+ derivatives, modified in the nicotinamide group, in a ternary complex with horse liver alcohol dehydrogenase.
European journal of biochemistry
confidence
Key findings
Molecular mechanics study of NAD+ analogues bound to LADH; no clinical or biological endpoints reported.
View source on PubMed (PMID 2970384) ↗
- Sample size
- 7 NAD+ analogues
- Population
- In silico molecular mechanics study (horse liver alcohol dehydrogenase/NAD+ analogues complex)
- Dosing
- Not applicable
- Duration
- Not applicable
- Route
- Not applicable
- Blinding
- not_reported
- Controls
- none
- Drug class
- coenzyme
Full abstract
The geometry of seven NAD+ analogues bound to horse liver alcohol dehydrogenase (LADH) modified only in their nicotinamide group, have been studied using AMBER molecular mechanics energy-minimization procedures. Starting geometries were taken from X-ray crystallographic data for NAD+/Me2SO/LADH reported by Eklund and co-workers. In this study the NAD+ analogues were encaged by the constituent amino acids of the enzyme within a range of 0.6 nm from the initial NAD+/Me2SO/Zn2+ complex. The calculational method used is able to rationalize individual substituent effects and to evaluate the essential interactions between NAD+ analogue, enzyme, Me2SO and Zn2+ without the necessity of additional X-ray data. The results presented here demonstrate that the reactivity of NAD+ derivatives as reported in literature can be qualitatively related to the position of the pyridine moiety in the active site.