Influencing Gαi/s Protein Activity by Peptidic Guanine Nucleotide Exchange Modulators

webinar

Fri, 21 May 2021, 16:00 CEST (Berlin)

Britta Nubbemeyer (Research group of Prof. Dr. Diana Imhof, University of Bonn)
Dr. Ajay Abisheck Paul George (BioSolveIT GmbH)

Influencing Gαi/s Protein Activity by Peptidic Guanine Nucleotide Exchange Modulators

For diseases such as cancer, the Gα subunits of heterotrimeric G proteins are attractive drug targets as alternatives to G protein-coupled receptors (GPCRs). Britta and Ajay contributed to the development of new modulators for the Gαi/s subfamilies providing insights into G protein-mediated signal transduction. In this work, two peptides were obtained that showed guanine-nucleotide exchange modulator (GEM)-like activity towards Gαi and Gαs in cell-based assays. This was complemented by an array of computational analyses ranging from homology modeling, detection of binding sites, molecular docking and molecular dynamics simulations.

This BioSolveIT webinar will cover ground on a wide spectrum of disciplines ranging from biochemistry, medicinal chemistry, to biomolecular modeling and simulations. First, Britta will show the selection of a promising peptide hit from a high-throughput screening approach and its further optimization with respect to drug-like properties, including the results from the activity assays of the lead structure and the optimized peptides. Ajay will then provide a plausible, molecular basis for the observed effects based on the computational investigations done. In summary, these results provide new insights into the G protein-mediated signal transduction and a further step towards specific targeting of the Gαi/s subunit by peptidic modulators.

Current news

category
Challenge
Martin Schwalm Emerges as Winner of Scientific Challenge Spring 2023
March 15, 2024 14:44 CET
The Scientific Challenge Spring 2023 comes to a conclusion: Martin Schwalm from the University of Frankfurt wins with his project “Identifying Binders to Hijack the Autophagy System for Targeted Protein Degradation”! The study aimed to identify binders for the LC3A protein’s hydrophobic binding site, a crucial target for drug discovery...
Read on
category
Software
Chemical Space Nagivation CLI Tool Updates
March 12, 2024 15:14 CET
Alongside infiniSee 6 ‘Echo’ we release updates to our command line tools that explore and create Chemical Spaces. Computational and tech-savvy medicinal chemists receive several powerful augmentations to the software; these help fine-tuning search parameters to perform even more efficient screening campaigns. New to those features are the new SMARTS...
Read on
category
Software
infiniSee 6 'Echo' Completes Trinity of Chemical Space Navigation
March 11, 2024 13:36 CET
We are more than proud to complete the trinity of Chemical Space navigation with the release of infiniSee Version 6, codenamed ‘Echo’! With Echo’s debut, a new feature called Motif Matcher has been introduced, enabling the screening of incredibly vast Chemical Spaces for compounds exhibiting high maximum common substructure (MCS)...
Read on