Molecular interaction of natural compounds with lipid bilayer membranes : Towards a better understanding of their biological and pharmaceutical actions

Overview & Synopsis

One of the key lockers to understand mechanisms of biological action of drugs and natural compounds is their capacity to incorporate/cross lipid bilayer membranes. In the light of demanding experimental techniques, in silico molecular modelling has become a powerful alternative to tackle these issues. In the past few years, molecular dynamics (MD) has opened many perspectives, providing an atomistic description of the related intermolecular interactions. Using MD simulations, we have explored the capacity of several compounds (polyphenols, vitamins E and C, plantazolicin, carprofens) to incorporate lipid bilayer membranes. The different compounds were chosen according to their different biological functions, namely (i) antioxidant activity against lipid peroxidation, (ii) antimicrobial activity with the possibility of trans-membrane pore formation, and (iii) inhibition of enzymes involved in Alzheimer’s disease. In order to rationalize their mechanisms of action, their position and orientation in membranes as well as their capacity to accumulate or permeate lipid bilayers were assessed. Having in mind a predictive purpose in drug design for MD simulations, the accuracy of the results relies on the quality of the in silico membrane models. By ensuring relationships between experimental and theoretical data, methodological improvements have been proposed. In particular, force field selection, xenobiotic parameterization and bilayer constitution emerged as crucial factors to appropriately depict drug-membrane interactions. For the latter issue, lipid mixtures e.g., including cholesterol have been developed.