Interaction of Lovastatin with Model Membranes by NMR Data and from MD Simulations

Abstract

© 2020, Springer Science+Business Media, LLC, part of Springer Nature. Lovastatin is a drug of the statin group which possesses the ability to decrease low-density lipoprotein cholesterol level by the competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. There is a hypothesis that pharmacological features of statins depend on their location in cell membrane, but to the present day, there is a lack of information in literature on interactions of statins with the surface of the cell membrane in liquid media. Intermolecular complex of lovastatin with dodecylphosphocholine (DPC) and sodium dodecylsulfate (SDS) micelles was investigated by NMR and computational methods. The results of NMR experiments and molecular dynamics (MD) simulation data showed that lovastatin forms intermolecular complexes with models of cell membranes in water solution. Locations of lovastatin on model membranes were established by NOESY NMR data. Distinctions in their positions can explain differences in pharmacological properties of studied compound.