Computational Methods are particularly useful in close combination with experimental techniques. This allows the direct input of latest experimental results into the model and vice versa. Therefore, we are developing models for calcium regulation or actin-myosin interaction in parallel to our fluorescence microscopy experiments.
Theoretical and computational methods may serve as a valuable 'hypothesis-maker' in biophysics and in recent years, advances in both algorithms and hardware have increased the importance of computer simulations.
For numerical studies, our group has assembled powerful hardware, including a dual-Xeon CPU Workstation and a workstation containing the recent i7 6850K and two Nvidia GTX 970 GPUs for GPU computing. Furthermore, our group has access to the bwUniCluster.
For our group, the ryanodine receptor (RyR) is particularly interesting. The ion channel is responsible for the release of Ca2+-ions from the sarcoplasmic reticulum (SR) into the myoplasm and hence plays a key role in the activation of skeletal muscle contraction. The receptor interacts closely with the DHP receptor and the cytoskeleton.
In the past, out group has performed molecular dynamics simulations on the luminal pore of RyR [e.g. Schilling R, Fink RH, Fischer WB (2014); Schilling R, Fink RH, Fischer WB (2016)]. Currently, we are interested in the opening/closing mechanism of the channel, as well as its conductivity and selectivity.
Calcium-ions inside the cell are present in various different "states". In addition to the free ions, calcium is also bound to several intrinsic and extrinsic calcium-binding sites (of which the fluorescence indicator is very often the most important one). Calcium-ions can also be sequestered in intracellular membrane-bound organelles, for example, mitochondria, the endoplasmic reticulum (ER), or the sarcoplasmic reticulum (SR) of muscle fibers.
All these parameters have to be taken into account for the development of suitable models for the complex process of intracellular calcium regulation. As only calcium ions bound to the fluorescence indicator can be experimentally measured, all other quantities have to be derived from these model calculations.