Molecular Dynamic Simulations of Biological Membranes

• Main Author: Waheed, Qaiser
• Format: Doctoral Thesis
• Language: English
• Published: KTH, Teoretisk biologisk fysik 2012
• Subjects: phospholipids; area compressibility; undulations; quantum corrections; cholesterol; phase transition; segregation
• Online Access: http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-102268; http://nbn-resolving.de/urn:isbn:978-91-7501-455-5

Biological membranes mainly constituent lipid molecules along with some proteins and steroles. The properties of the pure lipid bilayers as well as in the presence of other constituents (in case of two or three component systems) are very important to be studied carefully to model these systems and compare them with the realistic systems. Molecular dynamic simulations provide a good opportunity to model such systems and to study them at microscopic level where experiments fail to do. In this thesis we study the structural and dynamic properties of the pure phospholipid bilayers and the phase behavior of phospholipid bilayers when other constituents are present in them. Material and structural properties like area per lipid and area compressibility of the phospholipids show a big scatter in experiments. These properties are studied for different system sizes and it was found that the increasing undulations in large systems effect these properties. A correction was applied to area per lipid and area compressibility using the Helfrich theory in Fourier space. Other structural properties like order of the lipid chains, electron density and radial distribution functions are calculated which give the structure of the lipid bilayer along the normal and in the lateral direction. These properties are compared to the X-ray and neutron scattering experiments after Fourier transform. Thermodynamic properties like heat capacity and heat of melting are also calculated from derivatives of energies available in molecular dynamics. Heat capacity on the other hand include quantum effect and are corrected for that by applying quantum correction using normal mode analysis for a simple as well as ambiguous system like water. Here it is done for SPC/E water model. The purpose of this study is to further apply the quantum corrections on macromolecules like lipids by using this technique. Furthermore the phase behavior of two component systems (phospholipids/cholesterol) is also studied. Phase transition in these systems is observed at different cholesterol concentrations as a function of temperature by looking at different quantities (as an order parameter) like the order of chains, area per molecule and partial specific area. Radial distribution functions are used to look at the in plane structure for different phases having a different lateral or positional order. Adding more cholesterol orders the lipid chains changing a liquid disordered system into a liquid ordered one and turning a solid ordered system into a liquid ordered one. Further more the free energy of domain formation is calculated to investigate the two phasecoexistence in binary systems. Free energy contains two terms. One is bulk freeenergy which was calculated by the chemical potential of cholesterol moleculein a homogeneous system which is favorable for segregation. Second is thefree energy of having an interface which is calculated from the line tension of the interface of two systems with different cholesterol concentration which in unfavorable for domain formation. The size of the domains calculated from these two contributions to the free energy gives the domains of a few nm in size. Though we could not find any such domains by directly looking at our simulations. === <p>QC 20120913</p>