One of the most important aspects for all life on this planet is theact to keep their cellular processes in a state where they do notreach equilibrium. One part in the upholding of this imbalanced stateis the barrier between the cells and their surroundings, created bythe cell membrane. In addition to experiments, the investigation ofprocesses occuring in the cell membrane can be performed by usingmolecular dynamics simulations. Through this method we can obtain anatomistic description of the dynamics associated with events that arenot accessible to experimental setups. Molecular dynamics relies onthe integration of Newton's equations of motion in order to sample therelevant parts of phase-space for the system, and therefore it isdependent on a correct description of the interactions between all thesimulated particles. In this thesis I first present an improved methodfor the calculation of long-range interactions in molecular dynamicssimulations, followed by a study of cholesterol's impact on thepermeation of small solutes across a lipid bilayer. The first paper presents a previously derived modification to theparticle-mesh Ewald method, which makes it possible to apply thisto long-range Lennard-Jones interactions. Old implementations of themethod have been haunted by an extreme performance degradation andhere I propose a solution to this problem by applying a modifiedinteraction potential. I further show that the historical treatmentof long-range interactions in simulations of lipid bilayers hasnon-negligible effects on their structural properties.In the second paper, this modification is improved such that the smallerrors introduced by the modified interaction potential becomenegligible. Furthermore, I demonstrate that I have also improved theimplementation of the method so that it now only incurs a performanceloss of roughly 15% compared to conventional simulations using theGromacs simulation package.The third paper presents a simulation study of cholesterol's effect onthe permeation of six different solutes across a variety of lipidbilayers. I analyze the effect of different head groups, tail lengths,and tail saturation by performing simulations of the solutes in fourdifferent bilayers, with cholesterol contents between 0% and50%. Analysis of the simulations shows that the impact of the surfacearea per lipid on the partitioning of the solute could be lower thanpreviously thought. Furthermore, a model with a laterallyinhomogeneous permeability in cholesterol-containing membranes isproposed, which could explain the large differences betweenpermeabilities from experiments and calculated partition coefficientsin simulations. / <p>QC 20140609</p>
| Identifer | oai:union.ndltd.org:UPSALLA1/oai:DiVA.org:kth-145559 |
| Date | January 2014 |
| Creators | Wennberg, Christian L. |
| Publisher | KTH, Teoretisk biologisk fysik, Stockholm |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Licentiate thesis, comprehensive summary, info:eu-repo/semantics/masterThesis, text |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | TRITA-FYS, 0280-316X ; 2014:24 |
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