Biology subjects

Reuter, K.

Publications and source records attributed to Reuter, K..

3 recordsLinked to original sources

bioRxiv2023

Sensitive clustering of protein sequences at tree-of-life scale using DIAMOND DeepClust

The biosphere genomics era is transforming life science research, but existing methods struggle to efficiently reduce the vast dimensionality of the protein universe. We present DIAMOND DeepClust, an ultra-fast cascaded clustering method optimized to cluster the 19 billion protein sequences currently defining the protein biosphere. As a result, we detect 1.7 billion clusters of which 32% hold more than one sequence. This means that 544 million clusters represent 94% of all known proteins, illustrating that clustering across the tree of life can significantly accelerate comparative studies in the Earth BioGenome era.

genomics↗

bioRxiv2022

TriMem: A Parallelized Hybrid Monte Carlo Software for Efficient Simulations of Lipid Membranes

Lipid membranes are integral building blocks of living cells and perform a multitude of biological functions. Currently, molecular simulations of cellular-scale membrane structures at atomic resolution are nearly impossible, due to their size, complexity, and the large times-scales required. Instead, elastic membrane models are used to simulate membrane topologies and transitions between them, and to infer their properties and functions. Unfortunately, efficiently parallelized open-source simulation code to do so has been lacking. Here, we present TriMem, a parallel hybrid Monte Carlo simulation engine for triangulated lipid membranes. The kernels are efficiently coded in C++ and wrapped with Python for ease-of-use. The parallel implementation of the energy and gradient calculations and of Monte Carlo flip moves of edges in the triangulated membrane enable us to simulate also large and highly curved sub-cellular structures. For validation, we reproduce phase diagrams of vesicles with varying surface-to-volume ratios and area difference. The software can tackle a range of membrane remodelling processes on sub-cellular and cellular scales. Additionally, extensive documentation make the software accessible to the broad biophysics and computational cell biology communities.

biophysics↗

bioRxiv2020

The importance of charge in perturbing the aromatic glue stabilizing the protein-protein interface of homodimeric tRNA-guanine transglycosylase

Bacterial tRNA-guanine transglycosylase (Tgt) is involved in the biosynthesis of the modified tRNA nucleoside queuosine present in the anticodon wobble position of tRNAs specific for aspartate, asparagine, histidine and tyrosine. Inactivation of the tgt gene leads to decreased pathogenicity of Shigella bacteria. Therefore, Tgt constitutes a putative target for Shigellosis drug therapy. Since only active as homodimer, interference with dimer-interface formation may, in addition to active-site inhibition, provide further means to disable this protein. A cluster of four aromatic residues seems important to stabilize the homodimer. We mutated residues of this aromatic cluster and analyzed each exchange with respect to dimer and thermal stability or enzyme activity applying native mass spectrometry, thermal shift assay, enzyme kinetics, and X-ray crystallography. Our structural studies indicate strong influence of pH on homodimer stability. Obviously, protonation of a histidine within the aromatic cluster promotes the collapse of an essential structural motif within the dimer interface at slightly acidic pH. TOC GraphicFor table of contents use only. O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

molecular biology↗