Research Area A - Publications 2017

Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1862, Issue 4, Pages 800-807, https://doi.org/10.1016/j.bbagen.2017.12.007
Biochimica et Biophysica Acta, online article

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Background

Recently diphenyl-pyrazole (DPP) compounds and especially anle138b were found to reduce the aggregation of α-synuclein or Tau protein in vitro as well as in a mouse model of neurodegenerative diseases [1,2]. Direct interaction of the DPPs with the fibrillar structure was identified by fluorescence spectroscopy. Thereby a strong dependence of the ...

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Nature, volume 552, pages 84–87, doi:10.1038/nature24650
Nature, online article

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DNA nanotechnology, in particular DNA origami, enables the bottom-up self-assembly of micrometre-scale, three-dimensional structures with nanometre-precise features. These structures are customizable in that they can be site-specifically functionalized or constructed to exhibit machine-like or logic-gating behavio. Their use has been limited to applications that ...

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Nature, volume 552, pages 78–83, doi:10.1038/nature24651
Nature, online article

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Natural biomolecular assemblies such as molecular motors, enzymes, viruses and subcellular structures often form by self-limiting hierarchical oligomerization of multiple subunits. Large structures can also assemble efficiently from a few components by combining hierarchical assembly and symmetry, a strategy exemplified by viral capsids. De novo protein design ...

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The Journal of Chemical Physics, 147, 204107 (2017); https://doi.org/10.1063/1.4998647
The Journal of Chemical Physics, online article

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Direct random phase approximation (RPA) correlation energies have become increasingly popular as a post-Kohn-Sham correction, due to significant improvements over DFT calculations for properties such as long-range dispersion effects, which are problematic in conventional density functional theory. On the other hand, RPA still has various weaknesses, such as ...

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J. Chem. Theory Comput., 2017, 13 (11), pp 5479–5485, DOI: 10.1021/acs.jctc.7b00937
J. Chem. Theory Comput., online article

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An efficient scheme for the calculation of Born–Oppenheimer molecular dynamics (BOMD) simulations is introduced. It combines the corrected small basis set Hartree–Fock (HF-3c) method by Sure and Grimme [J. Comput. Chem. 2013, 43, 1672], extended Lagrangian BOMD (XL-BOMD) by Niklasson et al. [J. Chem. Phys. 2009, 130, 214109], and the calculation of the two ...

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The Journal of Chemical Physics, 147, 144101 (2017); https://doi.org/10.1063/1.4994190
The Journal of Chemical Physics, online article

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We introduce both rigorous and non-rigorous distance-dependent integral estimates for four-center two-electron integrals derived from a distance-including Schwarz-type inequality. The estimates are even easier to implement than our so far most efficient distance-dependent estimates [S. A. Maurer et al., J. Chem. Phys. 136, 144107 (2012)] and, in addition, do not ...

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PNAS, October 3, 2017. 201704937, https://doi.org/10.1073/pnas.1704937114
PNAS, online article

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Green fluorescent protein (GFP) variants are widely used as genetically encoded fluorescent fusion tags, and there is an increasing interest in engineering their structure to develop in vivo optical sensors, such as for optogenetics and force transduction. Ensemble experiments have shown that the fluorescence of GFP is quenched upon denaturation. Here we study ...

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Scientific Reports,volume 7, Article number: 12276, doi:10.1038/s41598-017-12519-9
Scientific Reports, online article

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The antibody Fv module which binds antigen consists of the variable domains VL and VH. These exhibit a conserved ß-sheet structure and comprise highly variable loops (CDRs). Little is known about the contributions of the framework residues and CDRs to their association. We exchanged conserved interface residues as well as CDR loops and tested the effects on two ...

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eLife 2017; 6:e27453, doi: 10.7554/eLife.27453
eLife, online article

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Segmented RNA viruses are ubiquitous pathogens, which include influenza viruses and rotaviruses. A major challenge in understanding their assembly is the combinatorial problem of a non-random selection of a full genomic set of distinct RNAs. This process involves complex RNA-RNA and protein-RNA interactions, which are often obscured by non-specific binding at ...

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Nature Methods, volume 14, pages 1090–1096 (2017), doi:10.1038/nmeth.4431
Nature Methods, online article

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Förster resonance energy transfer (FRET)-based tension sensor modules (TSMs) are available for investigating how distinct proteins bear mechanical forces in cells. Yet, forces in the single piconewton (pN) regime remain difficult to resolve, and tools for multiplexed tension sensing are lacking. Here, we report the generation and calibration of a genetically ...

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Chemistry - A European Journal, Volume23, Issue57, Pages 14267-14277, https://doi.org/10.1002/chem.201702423
Chemistry, online article

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Fluorescence‐based techniques are widely used to study biomolecular conformations, intra‐ and intermolecular interactions, and conformational dynamics of macromolecules. Especially for fluorescence‐based single‐molecule experiments, the choice of the fluorophore and labeling position are highly important. In this work, we studied the biophysical and structural ...

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Molecular Cancer Therapeutics, Volume 16, Issue 11, pp. 2329-2339, DOI: https://doi.org/10.1158/1535-7163.MCT-17-0129
Molecular Cancer Therapeutics, online article

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Epithelial–mesenchymal transition (EMT) induces tumor-initiating cells (TIC), which account for tumor recurrence, metastasis, and therapeutic resistance. Strategies to interfere with EMT are rare but urgently needed to improve cancer therapy. By using the myxobacterial natural compound Archazolid A as a tool, we elucidate the V-ATPase, a multimeric proton pump ...

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The Journal of Chemical Physics, 147, 024101 (2017); https://doi.org/10.1063/1.4990413
The Journal of Chemical Physics, online article

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An efficient implementation of energy gradients and of hyperfine coupling constants in second-order Møller-Plesset perturbation theory (MP2) is presented based on our fully atomic orbital (AO)-based approach. For the latter, an unrestricted AO-based MP2 formulation is introduced. A reduction in the dependency of the computational efficiency on the size of the ...

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J. Chem. Theory Comput., 2017, 13 (7), pp 3153–3159, DOI: 10.1021/acs.jctc.6b01166
J. Chem. Theory Comput., online article

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We present a parallel integral algorithm for two-electron contributions occurring in Hartree–Fock and hybrid density functional theory that allows for a strong scaling parallelization on inhomogeneous compute clusters. With a particular focus on graphic processing units, we show that our approach allows an efficient use of CPUs and graphics processing units ...

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The Journal of Chemical Physics, 146, 211106 (2017); https://doi.org/10.1063/1.4985085
The Journal of Chemical Physics, online article

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We present a method to improve upon the resolution-of-the-identity (RI) for correlation methods. While RI is known to allow for drastic speedups, it relies on a cancellation of errors. Our method eliminates the errors introduced by RI which are known to be problematic for absolute energies. In this way, independence of the error compensation assumption for ...

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J. Chem. Theory Comput., 2017, 13 (6), pp 2712–2716, DOI: 10.1021/acs.jctc.7b00515
J. Chem. Theory Comput., online online

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We present an extension of our graphics processing units (GPU)-accelerated quantum chemistry package to employ OpenCL compute kernels, which can be executed on a wide range of computing devices like CPUs, Intel Xeon Phi, and AMD GPUs. Here, we focus on the use of AMD GPUs and discuss differences as compared to CUDA-based calculations on NVIDIA GPUs. First ...

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PNAS, vol. 114, no. 23, 6040–6045, www.pnas.org/cgi/doi/10.1073/pnas.1619843114
PNAS, online article

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Owing to the cooperativity of protein structures, it is often almost impossible to identify independent subunits, flexible regions, or hinges simply by visual inspection of static snapshots. Here, we use single-molecule force experiments and simulations to apply tension across the substrate binding domain (SBD) of heat shock protein 70 (Hsp70) to pinpoint ...

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Journal of Cell Science (2017) 130, 1904-1916, doi:10.1242/jcs.201178
J Cell Sci., online article

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Vesicle transport is regulated at multiple levels including regulation by scaffolding proteins and the cytoskeleton. This tight regulation is essential since slowing or stoppage of transport can cause accumulation of obstacles and has been linked to diseases. Understanding the mechanisms by which transport is regulated as well as how motor proteins overcome ...

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The Journal of Chemical Physics, 146, 144108 (2017); https://doi.org/10.1063/1.4978476
The Journal of Chemical Physics, online article

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We present screening schemes that allow for efficient, linear-scaling short-range exchange calculations employing Gaussian basis sets for both CPU and GPU architectures. They are based on the LinK [C. Ochsenfeld et al., J. Chem. Phys. 109, 1663 (1998)] and PreLinK [J. Kussmann and C. Ochsenfeld, J. Chem. Phys. 138, 134114 (2013)] methods, but account for the ...

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ChemBioChem, Volume 18, Issue 13, Pages 1172–1176 , DOI: 10.1002/cbic.201600706
ChemBioChem, online article

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Mycobacterium tuberculosis (Mtb), the main causative agent of tuberculosis (Tb), has a complex cell envelope which forms an efficient barrier to antibiotics, thus contributing to the challenges of anti-tuberculosis therapy. However, the unique Mtb cell wall can be considered an advantage and be utilized to selectively label Mtb bacteria. Here we introduce three ...

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Science, Vol. 355, Issue 6331, eaam5488, DOI: 10.1126/science.aam5488
Science, online article

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Controlling the spatial arrangement of functional components in biological systems on the scale of higher-order macromolecular assemblies is an important goal in synthetic biology. Achieving this goal could yield new research tools and pave the way for interesting applications in health and biotechnology. DNA origami enables constructing arbitrary shapes on the ...

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J. Phys. Chem. Lett., 2017, 8 (7), pp 1585–1592, DOI: 10.1021/acs.jpclett.7b00371
J. Phys. Chem. Lett., online article

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Twisted intramolecular charge transfer (TICT) formation in hemithioindigo photoswitches has recently been reported and constitutes a second deexcitation pathway complementary to photoisomerization. Typically, this behavior is not found for this type of photoswitches, and it takes special geometric and electronic conditions to realize it. Here we present a ...

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J. Chem. Theory Comput., 2017, 13 (4), pp 1699–1705, DOI: 10.1021/acs.jctc.7b00157
J. Chem. Theory Comput., online article

 

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Eukaryotic RNA polymerase II catalyzes the transcription of DNA into mRNA very efficiently and with an extremely low error rate with regard to matching base and sugar moiety. Despite its importance, little is known about how it discriminates against 2′-deoxy NTPs during the chemical reaction. To investigate the differences in the addition reactions of ATP and ...

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J. Chem. Theory Comput., 2017, 13 (4), pp 1647–1655, DOI: 10.1021/acs.jctc.6b01235
J. Chem. Theory Comput., online article

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A reformulation of the random phase approximation within the resolution-of-the-identity (RI) scheme is presented, that is competitive to canonical molecular orbital RI-RPA already for small- to medium-sized molecules. For electronically sparse systems drastic speedups due to the reduced scaling behavior compared to the molecular orbital formulation are ...

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J. Chem. Theory Comput., 2017, 13 (3), pp 1102–1107, DOI: 10.1021/acs.jctc.6b00727
J. Chem. Theory Comput., online article

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The influence of embedding and coupling schemes on the convergence of the QM size in the QM/MM approach is investigated for the transfer of a proton in a DNA base pair. We find that the embedding scheme (mechanical or electrostatic) has a much greater impact on the convergence behavior than the coupling scheme (additive QM/MM or subtractive ONIOM). To achieve ...

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ACS Nano, 11 (2), pp 1498–1508, DOI: 10.1021/acsnano.6b06812
ACS Nano, online article

 

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Advances in the engineering of nanoparticles (NPs), which represent particles of less than 100 nm in one external dimension, led to an increasing utilization of nanomaterials for biomedical purposes. A prerequisite for their use in diagnostic and therapeutic applications, however, is the targeted delivery to the site of injury. Interactions between blood-borne ...

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PLoS ONE 12(1): e0170625, doi:10.1371/journal.pone.0170625
PLOS ONE, online article

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Protein-protein docking protocols aim to predict the structures of protein-protein complexes based on the structure of individual partners. Docking protocols usually include several steps of sampling, clustering, refinement and re-scoring. The scoring step is one of the bottlenecks in the performance of many state-of-the-art protocols. The performance of scoring ...

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eLife, 2017;6:e21477, doi: 10.7554/eLife.21477
eLife, online article

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ISWI-family nucleosome remodeling enzymes need the histone H4 N-terminal tail to mobilize nucleosomes. Here we mapped the H4-tail binding pocket of ISWI. Surprisingly the binding site was adjacent to but not overlapping with the docking site of an auto-regulatory motif, AutoN, in the N-terminal region (NTR) of ISWI, indicating that AutoN does not act as a simple ...

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PNAS, vol. 114, no. 5, 1015–1020, https://doi.org/10.1073/pnas.1612681114
PNAS, online article

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Stable anchoring of titin within the muscle Z-disk is essential for preserving muscle integrity during passive stretching. One of the main candidates for anchoring titin in the Z-disk is the actin cross-linker α-actinin. The calmodulin-like domain of α-actinin binds to the Z-repeats of titin. However, the mechanical and kinetic properties of this important ...

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