Biology subjects

Schmid, S.

Publications and source records attributed to Schmid, S..

2 recordsLinked to original sources

bioRxiv2018

nsearch: An open source C++ library for processing and similarity searching of next-generation sequencing data

Advancements in DNA sequencing technologies rapidly change the landscape of modern biology. The novel next-generation sequencing (NGS) applications often have special requirements regarding experimental data processing. Software tools developed and used for novel applications are generally designed for specific use cases and as such may be difficult to adapt to new uses. Simultaneously, software tools designed to be general are often difficult to adapt to special use cases.\n\nHere, we present nsearch, a modern open source C++11 library and command-line tool for biological sequence data processing. nsearch offers commonly used components for handling of biological sequences including paired-end read merging, quality filtering and sequence similarity searching. nsearch can either be embedded natively into other C++ applications or be packaged as a standalone executable.\n\nFunctionality and performance of nsearch is shown using benchmark data created using the Rfam 13 database. Benchmarking against common general purpose tools USEARCH and VSEARCH demonstrates that nsearch delivers performance comparable these state-of-the-art tools.\n\nnsearch is available on GitHub under the permissive BSD-3-clause license: https://github.com/stevschmid/nsearch

bioinformatics↗

bioRxiv2018

Effects of inhibitors on Hsp90’s conformational dynamics, cochaperone and client interactions

The molecular chaperone and heat-shock protein Hsp90 has become a central target in anti-cancer therapy. Nevertheless, the effect of Hsp90 inhibition is still not understood at the molecular level, preventing a truly rational drug design. Here we report on the effect of the most prominent drug candidates, namely radicicol, geldanamycin, derivatives of purine and novobiocin, on Hsp90s characteristic conformational dynamics and the binding of three interaction partners. Unexpectedly, the global opening and closing transitions are hardly affected by Hsp90 inhibitors. Instead, the conformational equilibrium, as well as the associated kinetic rate constants remain almost untouched. Moreover, we find no significant changes in the binding of the cochaperones Aha1 and p23 nor of the model substrate {Delta}131{Delta}. This holds true for both, competitive and allosteric inhibitors. Therefore, direct inhibition mechanisms, affecting only one molecular interaction, are unlikely. Based on our results, we speculate that the inhibitory action observed in vivo is caused by a combination of subtle effects, which can be used in the search for novel Hsp90 inhibition mechanisms.

biochemistry↗