Screening of HMG-CoA Reductase Inhibitors from Composite Salvia Miltiorrhiza Using Autodock

AimTo screen the inhibitors of HMG-CoA reductase from Composite Salvia Miltiorrhiza and explore the application of the virtual screening approach in the research of traditional Chinese medicine.MethodsA compound collection of Composite Salvia Miltiorrhiza was built including both natural compounds and metabolic products. Before Autodock was employed to screen the collection, three important docking parameters of Autodock were investigated in order to enhance the screening efficiency. The screening performance of Autodock was also evaluated by selecting and docking ten positive inhibitors whose experimental IC50 were available in MDDR database.ResultsA torsion-dependent strategy for docking parameter assignment was proposed based on parameter investigation, which improved the screening efficiency significantly. Performance evaluation indicated that the correlation coefficient (R2) between the predicted binding free energy and in vivo experimental IC50 was 0.865. Four phenolic acids were found to possess both quite low binding free energy and reasonable pose inside the binding site.ConclusionThe Composite Salvia Miltiorrhiza contains constituents possessing potential inhibitive activity against HMG-CoA reductase. It is a feasible way to screen the traditional Chinese medicine with virtual screening approach and the screening speed can be improved by the torsion-dependent assignment strategy.