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Molecules in Cell Membranes
Timr, Štěpán ; Jungwirth, Pavel (advisor) ; Böckman, Rainer (referee) ; Ettrich, Rüdiger (referee)
Biological membranes are actively involved in a multitude of processes in living cells; therefore, a detailed characterization of their structure, dynamics, and function is essential for an understanding of living organisms at the molecular level. In this work, we made use of the high spatial and temporal resolution offered by computer simulations to investigate the behavior of several molecular species which associate with cellular membranes. Using a combination of classical molecular dynamics simulations and ab initio electronic structure calculations, we were able to characterize nonlinear optical properties of membrane- embedded fluorescent probes and thus contribute to establishing two-photon polarization microscopy as a tool of structural biology. Moreover, our molecular dynamics simulations provided an atomistic picture of the reversible membrane binding of recoverin, a neuronal calcium-sensing protein involved in vision adaptation, and they also yielded an important insight into the mechanism of its calcium-induced myristoyl switch. In addition, we examined the biological role of cholesterol oxidation and compared two methods of representing transmembrane voltage in molecular dynamics simulations.
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Molecules in Cell Membranes
Timr, Štěpán ; Jungwirth, Pavel (advisor) ; Böckman, Rainer (referee) ; Ettrich, Rüdiger (referee)
Biological membranes are actively involved in a multitude of processes in living cells; therefore, a detailed characterization of their structure, dynamics, and function is essential for an understanding of living organisms at the molecular level. In this work, we made use of the high spatial and temporal resolution offered by computer simulations to investigate the behavior of several molecular species which associate with cellular membranes. Using a combination of classical molecular dynamics simulations and ab initio electronic structure calculations, we were able to characterize nonlinear optical properties of membrane- embedded fluorescent probes and thus contribute to establishing two-photon polarization microscopy as a tool of structural biology. Moreover, our molecular dynamics simulations provided an atomistic picture of the reversible membrane binding of recoverin, a neuronal calcium-sensing protein involved in vision adaptation, and they also yielded an important insight into the mechanism of its calcium-induced myristoyl switch. In addition, we examined the biological role of cholesterol oxidation and compared two methods of representing transmembrane voltage in molecular dynamics simulations.
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Simulation of processes in cellular membranes
Timr, Štěpán ; Jungwirth, Pavel (advisor) ; Pittner, Jiří (referee)
Probing orientations of fluorescent molecules embedded in or attached to cell membranes has a great potential to reveal information on membrane structure and processes occurring in living cells. In this thesis, we first describe one- and two-photon linear dichroism measurements on a fluorescent probe embedded in a phospholipid membrane with a well- defined lipid composition. On the basis of experimental data, we determine the distribution of the angle between the one-photon transition dipole moment of the probe and the membrane normal. At the same time, we perform molecular dynamics simulations of the fluorescent probe and quantum calculations of its one-photon and two-photon absorption properties. By comparing the orientational distribution gained from experiments with that predicted by simulations, we test the ability of linear dichroism measurements to report on the orientation of a fluorescent molecule in a lipid membrane. We also examine the applicability of molecular simulations as a basis for the interpretation of experimental data.
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