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Voltage-gated sodium channels have essential roles in electrical signalling. Prokaryotic sodium channels are tetramers consisting of transmembrane (TM) voltage-sensing and pore domains, and a cytoplasmic carboxy-terminal domain. Previous crystal structures of bacterial sodium channels revealed the nature of their TM domains but not their C-terminal domains(More)
Inward rectifier (Kir) potassium channels are characterized by two transmembrane helices per subunit, plus an intracellular C-terminal domain that controls channel gating in response to changes in concentration of various ligands. Based on the crystal structure of the tetrameric C-terminal domain of Kir3.1, it is possible to build a homology model of the(More)
—The reproduction and replication of novel results has become a major issue for a number of scientific disciplines. In computer science and related computational disciplines such as systems biology, the issues closely revolve around the ability to implement novel algorithms and approaches. Taking an approach from the literature and applying it to a new(More)
Molecular dynamics simulations can now routinely generate data sets of several hundreds of gigabytes in size. The ability to generate this data has become easier over recent years and the rate of data production is likely to increase rapidly in the near future. One major problem associated with this vast amount of data is how to store it in a way that it(More)
Bacterial chemoreceptors provide an important model for understanding signalling processes. In the serine receptor Tsr from E. coli, a binding event in the periplasmic domain of the receptor dimer causes a shift in a single transmembrane helix of roughly 0.15 nm towards the cytoplasm. This small change is propagated through the ≈ 22 nm length of the(More)
The use of molecular simulation to estimate the strength of macromolecular binding free energies is becoming increasingly widespread, with goals ranging from lead optimization and enrichment in drug discovery to person-alizing or stratifying treatment regimes. In order to realize the potential of such approaches to predict new results, not merely to explain(More)
Conformational change in polymers including proteins is central to many molecular processes. Defining conformational states, however, remains a difficult and increasingly common problem, with many existing methods based on arbitrary or potentially unrepresentative measures. Furthermore, the expanding length of molecular dynamics simulations and direct(More)
A statistical approach based on the Wigner transform is proposed for the description of partially incoherent optical wave dynamics in nonlinear media. An evolution equation for the Wigner transform is derived from a nonlinear Schrödinger equation with arbitrary nonlinearity. It is shown that random phase fluctuations of an incoherent plane wave lead to a(More)
The stability of biological models is an important test for establishing their soundness and accuracy. Stability in biological systems represents the ability of a robust system to always return to homeosta-sis. In recent work, modular approaches for proving stability have been found to be swift and scalable. If stability is however not proved, the currently(More)
Caenorhabditis elegans vulval development is a paradigm system for understanding cell differentiation in the process of organogenesis. Through temporal and spatial controls, the fate pattern of six cells is determined by the competition of the LET-23 and the Notch signalling pathways. Modelling cell fate determination in vulval development using state-based(More)