Two Dimensional Window Exchange Umbrella Sampling for Transmembrane Helix Assembly

The method of window exchange umbrella sampling molecular dynamics (WEUSMD) with a pre-optimized parameter set was recently used to obtain the most probable conformations and the energetics of transmembrane (TM) helix assembly of a generic TM sequence. When applied to glycophorin A TM domain (GpA-TM) using the restraint potentials along the helix-helix distance, however, tight interfacial packing of GpA-TM resulted in insufficient conformational sampling at short helix-helix separation. This sampling issue is addressed by extending the WEUSMD into two dimensions with the restraint potentials along the helix-helix distance and crossing angle. The two-dimensional WEUSMD results demonstrate that the incomplete sampling in the one-dimensional WEUSMD arises from high barriers along the crossing angle between the GpA-TM helices. Together with the faster convergence in both the assembled conformations and the potential of mean force, the 2D-WEUSMD can be a general and efficient approach in computational studies of TM helix assembly

Development and quality characterization of a novel CT system.

Novel geometrical designs of computed tomography (CT) scanners in combination with novel image reconstruction algorithms promise to reduce ionizing radiation exposure to the patient in CT scans. While the sampling density of the Field Of View (FOV) is retained, the image quality can even be increased in contrast to conventional CT scanners. In this study, we present first images obtained with a novel CT scanner that we developed in our working group. In this open CT system with irradiation within a fan beam, parallel Radon data are directly obtained for image reconstruction using the OPED (Orthogonal Polynomial Expansion on the Disk) algorithm. This algorithm uses Radon data directly, i.e., without any further data processing such as rebinning and interpolation. We experimentally test theoretical predictions for this system by quantifying image quality parameters in comparison with corresponding parameters that are derived from the images of a conventional scanner of the 3rd generation. The modulation transfer function (MTF) and noise power spectrum (NPS) are determined using a test phantom. The novel CT system quantitatively shows the same noise property as the conventional scanner. The resolution that is reached in the center of a reconstructed image is nearly identical for both scanner types. But we found that the resolution that is achieved in the novel CT system does not depend on the image position while the MTF of the conventional scanner decreases for radially outer regions of the image