Several natural plant extracts and pharmacological drugs are biologically active as antidepressant, antimicrobial, anticancer and anti-inflammatory agents. The diverse healing properties of these compounds and the equivalent efficacy of their optical isomers suggest that their activity might be exerted via modulation of membrane properties and of transmembrane proteins residing therein. The interactions of these small molecules with lipid bilayers and membrane proteins are examined using MD simulations. The goal is to (1) drive the design of affordable new anticancer and antimicrobial agents to counter the problem of multidrug resistance in pathogens and cancer cells (2) Obtain insights into the mechanism of action of natural plant extracts of medicinal value, which are being used in Eastern medicine for millenia.

Examples of such molecules include the Indian spice extract: curcumin, which gives Indian food its characteristic yellow color; and cyclic terpenes: compounds present in citrus fruits and the leaves of the plant Perilla frutescens: an Asian garnish popularly used in sushi.

Left: Interactions between a seramesine drug molecule and a phosholipid headgroup. Right: Insertion of Perilla extracts with a phospholipid bilayer

Relevant Publications

Kopec, W., and Khandelia, H. (2014) Reinforcing the membrane-mediated mechanism of action of the anti-tuberculosis candidate drug thioridazine with molecular simulations, J. Comput. Aided Mol. Des. 28, 123-134.

Kopec, W., Telenius, J., and Khandelia, H. (2013) Molecular dynamics simulations of the interactions of medicinal plant extracts and drugs with lipid bilayer membranes, Febs Journal 280, 2785-2805.

Khandelia, H.*, Witzke, S. and Mouritsen, O.G. (2010) Interaction of Salicylate and a Terpenoid Plant Extract with Model Membranes: Reconciling Experiments and Simulations. Biophys. J.

Witzke, S., Duelund, L., Pedersen, M., Kongsted, J., Mouritsen, O.G. and Khandelia, H.* (2010 Nov 11) The inclusion of terpenoid plant extracts in lipid bilayers investigated by molecular dynamics simulations. J. Phys. Chem. B .

Parry, M.J., Alakoskela, J.M., Khandelia, H., Kumar, S.A., Jaattela, M., Mahalka, A.K. and Kinnunen, P.K. (2008) High-affinity small molecule-phospholipid complex formation: binding of siramesine to phosphatidic acid. J. Am. Chem. Soc.