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Laboratory of Molecular Biophysics
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Integral membrane proteins account for ca. 30% of all genes. They are responsible for a diversity of functions, including signalling and transport across membranes. Recent advances in membrane protein crystallography have significantly enhanced our knowledge of membrane protein structures. However, to understand the relationship between structures and biological functions, it is necessary to characterise the dynamics of membrane proteins in the complex, anisotropic environment provided by a lipid bilayer. We are using computational approaches to explore the conformational dynamics of membrane proteins, to relate their dynamic properties to their biological functions, and to refine methods of structure prediction for application to those membrane proteins (the vast majority) for which experimental structural data remain unavailable.
Ion channels mediate electrical excitability in neurons and muscle. Three-dimensional structures for channels may be combined with computer simulations to permit rigorous exploration of structure-function relations of channels. By combining atomistic simulations (in which all atoms of the channel molecule, water and ions are treated explicitly) with continuum methods (in which the description of the channel system is considerably simplified) it is possible to simulate some of the physiological properties of channels. An overview of this work is provided in [1].
In addition to simulation studies of a number of ion channels, we are also interested in applying these, and related, computational approaches to other membrane proteins, including a number of transporters, both bacterial and mammalian. Methods being employed include: structural bioinformatics; molecular modelling on the basis of sparse structural data; and simulations based on experimental structures and homology models.
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