Research interests
Cholesterol - Membrane Interactions
Cholesterol and other biologically important sterols play a significant role in the function and
dynamics of plasma membranes in the cells. Research over the past decades revealed that cholesterol optimizes the
physical properties of plasma membranes in eukaryotic cells, as it regulates membrane fluidity and permeability and
adjusts the lateral mobility of membrane proteins. Ergosterol can be found in the membranes of fungi, yeasts and protozoans
and lanosterol is the major constituent of prokaryotic cell membranes and the evolutionary precursor of cholesterol.
Although the two last-mentioned sterols are structurally very similar to cholesterol, only cholesterol has been shown to
provide the maximum optimization of the membrane. Major questions remain unanswered concerning the interactions between
cholesterol and lipids or how cholesterol is organised in the membranes and also which are the particular characteristics
of cholesterol, which led to its selection through evolution even though its precursors are structurally very similar.
In the past few years, a growing number of theoretical studies, which use simulation techniques, with the help of
"model membranes" attempt to answer the above-mentioned questions. However, to our knowledge, most empirical force
fields that are being currently used in common MD packages are equipped with parameter sets for modeling biomolecules but
none have been thoroughly developed for biologically important sterols, such as cholesterol. Therefore, to better and more
accurately model the physical properties of sterols, it has been considered necessary to develop a new parameter set for
cholesterol, ergosterol and lanosterol using an automated refinement method. The parameters derived have been
incorporated in the CHARMM force field. Parameter sets are designed to fit results of quantum chemical calculations.
We perform MD simulations of hydrated sterol:lipid systems (cholesterol, ergosterol and lanosterol, respectively)
to illustrate the effect of different sterols on the structure and dynamics of the lipid bilayer. The results show different
ordering effects of the hydrocarbon chains upon addition of the different sterols and with respect to their orientation in the
pure bilayer. Different sterol hydration levels and their effect on the trans/gauche population of the lipid alkyl chains are
also present.
Publication list:
- Z. Cournia, G.M. Ullmann and J.C. Smith, "Differential effects of cholesterol, ergosterol and lanosterol on a dipalmitoyl phosphatidylcholine (DPPC) membrane: A Molecular Dynamics Simulation Study", JPCB (2006), accepted for publication
- Z. Cournia, J.C. Smith and G.M. Ullmann, "A molecular mechanics force-field for biologically-important sterols",
J.Comp.Chem., 26 (2005), pp.1383-1399
- A.C. Vaiana, Z. Cournia, I.B. Costescu and J.C. Smith, "AFMM: A molecular mechanics force field vibrational
parametrization program'", Computer Physics Communications, 167 (2005), pp.34-42
- Z.Cournia, G.M. Ullmann and J.C. Smith, "Molecular Dynamics ofCholesterol in Biomembranes", Lecture Series on
Computer and Computational Sciences, VSP International, Vol. 1 (2004), pp.131-135
- Z. Cournia, A.C. Vaiana, J.C. Smith, G.M. Ullmann, "Derivation of a Molecular Mechanics Force Field for Cholesterol",
Pure Appl.Chem., Vol.76, pp.189-196,2004
- J.C. Smith, Z. Cournia, A.Taly, A.L. Tournier, D.Mihailescu, G.M. Ullmann,
"Conformational Changes in Proteins and Membranes", In: Novel Approaches to the Structure and Dynamics of Liquids:
Experiments, Theories and Simulations. Eds. J. Samios, V.A.Durov, Kluwer Academic Publishers, Dordrecht: 485-502, 2004
- Z.Cournia, "Glass-like behavior in supercritical fluids: The effect of critical slowing down on solute dynamics
using the computational technique of Molecular Dynamics simulations", Diploma Thesis, Dept. of Physical Chemistry,
University of Athens, Greece
- Z. Cournia, "Is NGC 1938 and NGC 1939 a binary cluster?", Acta Physica Polonica A, 1995, 88, Suppl.
Conference List and Invited Talks
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