Termine WintERSEMESTER 2023/24
Aufgrund einer möglichen Corona-Pandemie finden die Vorträge zur Zeit sowohl als Zoom-Meetings als auch wahlweise in Präsenz (Hybridveranstaltungen) statt. Sie finden die Daten zur Einwahl in das Zoom-Meeting bei dem jeweiligen Vortrag.
Dienstag, 24.10.2023, 18 Uhr C. t.
Referent: Prof. Dr. Marcel Bemúdez, Institute of Pharmaceutical and Medicinal Chemistry, University of Münster
Thema: A dynamic view on receptor-ligand interactions
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Meeting ID: 621 2506 6616
Ligands for G protein-coupled receptors (GPCRs) represent the largest class of marketed dugs and are essential therapeutics for a plethora of clinical indications. Surprisingly, almost all of them have been developed under the assumption that GPCRs are simple on-off switches. Over the last decade specific receptor-ligand complexes were determined by crystallography or cryo-EM providing an indispensable structural view on this protein class. However, the resulting atomic models represent single static and energetically favoured conformations of highly flexible receptors. For a mechanistic understanding of ligand-dependent receptor functionality we need to consider GPCR-ligand complexes as dynamic entities.
Here, we report use cases of a fully-automated approach to combine three-dimensional pharmacophore models with molecular dynamics (MD) simulations: dynophores. This technique allows us to trace receptor-ligand interactions in space and time throughout the MD trajectory and provides a perfect tool for the communication with pharmacologists and chemists. Subtle changes in binding modes and interaction frequencies can be analysed and quantitatively compared providing a way to rationally explain how ligand binding to a receptor triggers a distinct pharmacological effect.
We will showcase how the application of dynophores helped us to mechanistically understand complex pharmacological functionalities including subtype selectivity, partial agonism and biased signalling.
Dienstag, 16.01.2024, 18 Uhr c. t.
Referent: Prof. Dr. Sebastian Günther, Universität Greifswald, Pharmaceutical Biology, Institute of Pharmacy
Thema: Antibiofilm Activity of Polyphenols against Multidrug-Restistant Escherichia coli Strains
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Meeting ID: 680 8031 9896
Multidrug-resistant gram-negative pathogens like Escherichia coli have become increasingly challenging to treat, necessitating the exploration of alternative treatment options. Targeting virulence factors such as biofilm formation could be one such avenue. Inhibition of biofilm-related structures like curli and cellulose formation in E. coli has been demonstrated with various phenolic natural compounds, such as epigallocatechin gallate. To assess whether structurally distinct compounds, namely octyl gallate, scutellarein, and wedelolactone influence common pathways of biofilm formation in E. coli, a comprehensive comparative RNA-sequencing approach was adopted, supplemented by RT-qPCR to gain initial insights into the affected pathways at the transcriptomic level. Bioinformatic analysis of the RNA-Seq data was conducted using DESeq2, BioCyc, and KEGG Mapper. The comparative bioinformatics analysis of pathways revealed that, regardless of their structure, all compounds predominantly impacted similar biological processes. These pathways included bacterial motility, chemotaxis, biofilm formation, as well as metabolic processes such as arginine biosynthesis and the tricarboxylic acid cycle. Overall, this study provides the initial insights into the potential mechanisms of action of novel phenolic biofilm inhibitors and underscores the intricate regulatory processes involved in biofilm formation in E. coli.
48149 Münster statt. ! Aktuell auch als Zoom-Meetings!