Distribution of Articles published per year
(2013 - 2018)
(2013 - 2018)
Total number of journals
Article 0 Reads 0 Citations New insights into the structural dynamics of the kinase JNK3. Published: 21 June 2018
Scientific Reports, doi: 10.1038/s41598-018-27867-3
In this work, we study the dynamics and the energetics of the all-atom structure of a neuronal-specific serine/threonine kinase c-Jun N-terminal kinase 3 (JNK3) in three states: unphosphorylated, phosphorylated, and ATP-bound phosphorylated. A series of 2 µs atomistic simulations followed by a conformational landscape mapping and a principal component analysis supports the mechanistic understanding of the JNK3 inactivation/activation process and also indicates key structural intermediates. Our analysis reveals that the unphosphorylated JNK3 undergoes the 'open-to-closed' movement via a two-step mechanism. Furthermore, the phosphorylation and ATP-binding allow the JNK3 kinase to attain a fully active conformation. JNK3 is a widely studied target for small-drugs used to treat a variety of neurological disorders. We believe that the mechanistic understanding of the large-conformational changes upon the activation of JNK3 will aid the development of novel targeted therapeutics.
Article 2 Reads 2 Citations PubMedPortable: A Framework for Supporting the Development of Text Mining Applications. Published: 05 October 2016
PLOS ONE, doi: 10.1371/journal.pone.0163794
Information extraction from biomedical literature is continuously growing in scope and importance. Many tools exist that perform named entity recognition, e.g. of proteins, chemical compounds, and diseases. Furthermore, several approaches deal with the extraction of relations between identified entities. The BioCreative community supports these developments with yearly open challenges, which led to a standardised XML text annotation format called BioC. PubMed provides access to the largest open biomedical literature repository, but there is no unified way of connecting its data to natural language processing tools. Therefore, an appropriate data environment is needed as a basis to combine different software solutions and to develop customised text mining applications. PubMedPortable builds a relational database and a full text index on PubMed citations. It can be applied either to the complete PubMed data set or an arbitrary subset of downloaded PubMed XML files. The software provides the infrastructure to combine stand-alone applications by exporting different data formats, e.g. BioC. The presented workflows show how to use PubMedPortable to retrieve, store, and analyse a disease-specific data set. The provided use cases are well documented in the PubMedPortable wiki. The open-source software library is small, easy to use, and scalable to the user's system requirements. It is freely available for Linux on the web at https://github.com/KerstenDoering/PubMedPortable and for other operating systems as a virtual container. The approach was tested extensively and applied successfully in several projects.
Article 0 Reads 3 Citations Discovery of the Inhibitory Effect of a Phosphatidylinositol Derivative on P-Glycoprotein by Virtual Screening Followed ... Published: 09 April 2013
PLOS ONE, doi: 10.1371/journal.pone.0060679
P-glycoprotein is capable of effluxing a broad range of cytosolic and membrane penetrating xenobiotic substrates, thus leading to multi-drug resistance and posing a threat for the therapeutic treatment of several diseases, including cancer and central nervous disorders. Herein, a virtual screening campaign followed by experimental validation in Caco-2, MDKCII, and MDKCII mdr1 transfected cell lines has been conducted for the identification of novel phospholipids with P-gp transportation inhibitory activity. Phosphatidylinositol-(1,2-dioctanoyl)-sodium salt (8∶0 PI) was found to significantly inhibit transmembrane P-gp transportation in vitro in a reproducible-, cell line-, and substrate-independent manner. Further tests are needed to determine whether this and other phosphatidylinositols could be co-administered with oral drugs to successfully increase their bioavailability. Moreover, as phosphatidylinositols and phosphoinositides are present in the human diet and are known to play an important role in signal transduction and cell motility, our finding could be of substantial interest for nutrition science as well.