241
Chapter 8
Molecular Dynamics Simulations of Lipid
Bilayers with Incorporated Peptides
Milan Melicherčík, Tibor Hianik and Ján Urban
© Springer Science+Business Media Dordrecht 2014
L. Gorb et al. (eds.), Application of Computational Techniques in Pharmacy and Medicine,
Challenges and Advances in Computational Chemistry and Physics 17,
DOI 10.1007/978-94-017-9257-8_8
M. Melicherčík () · T. Hianik · J. Urban
Department of Nuclear Physics and Biophysics, Faculty of Mathematics,
Physics and Informatics, Comenius University, Mlynská dolina,
Bratislava, Slovak Republic 842 48, Europe
e-mail: milan.melichercik@fmph.uniba.sk
Abstract Biological membranes are important cell structures that play important role in the transport of the ions and other molecules into and out of the cell
and regulate the signaling pathway. They are composed of lipid bilayer, integral
and peripheral proteins. The ionic channels, enzymes and most of the membrane
receptors belong to integral proteins that span the membrane and contact by their
hydrophobic part with hydrophobic interior of the lipid bilayer. These hydrophobic
interactions are crucial for the effect of peptide on a lipid bilayer matrix and vice
versa. The study of the mechanisms of these interactions is important for understanding the functioning of the peptides in a membrane. However the study of
native biomembrane is rather complicated due to its complexity and inhomogeneity.
Therefore model lipid bilayers and short peptides can be used as a model for study
of the protein–lipid interactions. In this chapter we review the current state of the
art in experimental and molecular dynamics simulation study of the short peptide–
membrane interactions. As an example we consider in more detail the application
of molecular dynamic simulations on the study of interaction of a model lysineflanked α-helical peptides P 24 , LA 12 , L 24 and its analogues A 24 , I 24 , and V 24 with
lipid bilayers composed of dimyristoylphosphatidylcholine (DMPC) and dipalmitoylphosphatidylcholine (DPPC) both in a gel and in a liquid-crystalline state. We
have shown that these peptides cause disordering of the lipid bilayer in the gel state
and small changes in a liquid-crystalline state. The peptides affect ordering of the
surrounding lipids depending on the helix stability, the amount of dihedral angles
in trans conformation and the number of transitions between trans and gauche conformation. It has been found the tendency of Lys-flanked peptides to compensate
the positive mismatch between peptide and membrane hydrophobic core by tilting.
Chapter 8
Molecular Dynamics Simulations of Lipid
Bilayers with Incorporated Peptides
Milan Melicherčík, Tibor Hianik and Ján Urban
© Springer Science+Business Media Dordrecht 2014
L. Gorb et al. (eds.), Application of Computational Techniques in Pharmacy and Medicine,
Challenges and Advances in Computational Chemistry and Physics 17,
DOI 10.1007/978-94-017-9257-8_8
M. Melicherčík () · T. Hianik · J. Urban
Department of Nuclear Physics and Biophysics, Faculty of Mathematics,
Physics and Informatics, Comenius University, Mlynská dolina,
Bratislava, Slovak Republic 842 48, Europe
e-mail: milan.melichercik@fmph.uniba.sk
Abstract Biological membranes are important cell structures that play important role in the transport of the ions and other molecules into and out of the cell
and regulate the signaling pathway. They are composed of lipid bilayer, integral
and peripheral proteins. The ionic channels, enzymes and most of the membrane
receptors belong to integral proteins that span the membrane and contact by their
hydrophobic part with hydrophobic interior of the lipid bilayer. These hydrophobic
interactions are crucial for the effect of peptide on a lipid bilayer matrix and vice
versa. The study of the mechanisms of these interactions is important for understanding the functioning of the peptides in a membrane. However the study of
native biomembrane is rather complicated due to its complexity and inhomogeneity.
Therefore model lipid bilayers and short peptides can be used as a model for study
of the protein–lipid interactions. In this chapter we review the current state of the
art in experimental and molecular dynamics simulation study of the short peptide–
membrane interactions. As an example we consider in more detail the application
of molecular dynamic simulations on the study of interaction of a model lysineflanked α-helical peptides P 24 , LA 12 , L 24 and its analogues A 24 , I 24 , and V 24 with
lipid bilayers composed of dimyristoylphosphatidylcholine (DMPC) and dipalmitoylphosphatidylcholine (DPPC) both in a gel and in a liquid-crystalline state. We
have shown that these peptides cause disordering of the lipid bilayer in the gel state
and small changes in a liquid-crystalline state. The peptides affect ordering of the
surrounding lipids depending on the helix stability, the amount of dihedral angles
in trans conformation and the number of transitions between trans and gauche conformation. It has been found the tendency of Lys-flanked peptides to compensate
the positive mismatch between peptide and membrane hydrophobic core by tilting.