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Until recently proteins were considered as nature’s robots performing both unique chemical transformations or specifically interacting with their cognate binding partners under environmental conditions suitable for living organisms. Common understanding is that these functionalities rely on the existence of stably folded protein scaffolds. This structure-function paradigm, however, has been put in question: it is now acknowledged that an increasing number of proteins are lacking stably folded tertiary structures and that this intrinsic flexibility contributes to their biological functionality. The emerging picture is that proteins have evolved to substantially increase the diversity of their conformational ensembles and that even in seemingly random-coil-like disordered proteins there is a hidden structural simplicity that needs to be addressed by appropriate experimental techniques and theoretical concepts which grasp the essential properties of the underlying structural components.
A hallmark of our research is the integrative application of a novel computational biology concept (meta-structure concept) and information-rich NMR spectroscopy directed towards a better understanding of the underlying mechanisms of important biological problems. Finally, as much of protein function is predicated on dynamics, we are developing novel methodological approaches which combine biochemistry, bioorganic chemistry and NMR spectroscopy to unravel the microscopic details of functionally important protein plasticity with potential applications also in drug development programs.
Robert Konrat studied Chemistry in Graz, Austria, and did postdoctoral research at the Université de Lausanne and University of Toronto. He held faculty positions at the University of Innsbruck and visiting professorships at the École Normale Supérieur, Paris, France, University of Barcelona, Spain and the University of California, San Diego, USA.
VBC5
Room: 1.602
+43 1 4277 52202
Correlated structural fluctuations in IDPs are probed by a novel NMR technique developed in our laboratory employing cross-correlated paramagnetic spin relaxation. An application to the Osteopontin-Heparin complex revealed unprecedented details of structural adaptations upon polysaccharide binding.
A novel technique was developed to probe protein-receptor binding in living cells. By combining advanced cell biology and sophisticated NMR techniques unique information about receptor-binding sites can be obtained that allows the determination of IDP-receptor complexes in native environments.
A central theme of the laboratory is to overcome the dichotomy of globular proteins and IDPs. To this end, we have developed computational and NMR techniques that unravel hidden structural compaction in IDPs. The IDP-region of CFTR partly exists in a compact state that facilitates binding to the structured nucleotide-binding domain.
We have developed a versatile prediction method of identifying protein targets and the identification of novel chemical scaffolds for protein targets exclusively based on primary sequence information of the protein (meta-structure) or a 2D representation of the small molecule (Shannon-Entropy Descriptor, SHED).
Our integrated methods platform offers exciting possibilities in biomedical research: identification of novel drugs and their targets, drug repurposing, pathway and mode of action analysis of drugs. Finally, preliminary big data analysis of existing drugs has revealed a surprising hidden relationship among different disease areas.
Sonja Knödlstorfer
PhD Student +43 1 4277 52260
Room: 0122
Robert Konrat
Group Leader +43 1 4277 52202
Room: 1.602
Georg Kontaxis
Staff Scientist +43 1 4277 52218
Room: 1.608
Karin Ledolter
Lab Manager +43 1 4277 52260
Room: 0122
Mario Migotti
PhD Student +43 1 4277 52263
Room: 0.114
Aleksandra Ptaszek
PhD Student +43 1 4277 52229
Room: 0614
Thomas Schwarz
Senior PostDoc +43 1 4277 52263
Room: 0.114
High-resolution structural information of membrane-bound α-synuclein provides insight into the MoA of the anti-Parkinson drug UCB0599.
Schwarz Thomas C, Beier Andreas, Ledolter Karin, Gossenreiter Thomas, Höfurthner Theresa, Hartl Markus, Baker Terry S, Taylor Richard J, Konrat Robert
The Anti-Histamine Azelastine, Identified by Computational Drug Repurposing, Inhibits Infection by Major Variants of SARS-CoV-2 in Cell Cultures and Reconstituted Human Nasal Tissue.
Konrat Robert, Papp Henrietta, Kimpel Janine, Rössler Annika, Szijártó Valéria, Nagy Gábor, Madai Mónika, Zeghbib Safia, Kuczmog Anett, Lanszki Zsófia, Gesell Tanja, Helyes Zsuzsanna, Kemenesi Gábor, Jakab Ferenc, Nagy Eszter
PI by NMR: Probing CH-π Interactions in Protein-Ligand Complexes by NMR Spectroscopy.
Platzer Gerald, Mayer Moriz, Beier Andreas, Brüschweiler Sven, Fuchs Julian E, Engelhardt Harald, Geist Leonhard, Bader Gerd, Schörghuber Julia, Lichtenecker Roman, Wolkerstorfer Bernhard, Kessler Dirk, McConnell Darryl B, Konrat Robert
Compensatory adaptations of structural dynamics in an intrinsically disordered protein complex.
Kurzbach Dennis, Schwarz Thomas C, Platzer Gerald, Höfler Simone, Hinderberger Dariush, Konrat Robert
Project title: "NMR investigations of the hyperphosphorylated IDP Osteopontin" (P28359)
Project title: “Structural Dynamics of IDPs probed by Cross-Correlated NMR Spin Relaxation" (P 28359)
LS17-008, Structure Zoom (as Co-PI with Christian Becker)
ITN: FLUOR21 participant
2016-2019: The Group Konrat participates in the special Doctoral Program "Integrative Structural Biology" reviewed and funded by the Austrian Science Fund FWF.
Novartis, Boehringer-Ingelheim, UCB, Alkahest, IDPharma, Everpharma, Neuropore
Project-leader: Robert Konrat
Business partner: Boehringer Ingelheim RCV GmbH & Co KG
Duration: 01.02.2017 - 31.01.2025
CD Laboratory for knowledge-based structural biology and biotechnology
Christian Doppler Research Association
University of Vienna
Description: The scientists will primarily investigate protein structure, which is crucial for the development of new therapeutic methods for a great variety of diseases ranging from Alzheimer’s and infectious diseases to cancer. This renders it a most valuable tool in biomedical research. In order to gain new insights into protein structure, function and interactions that could potentially be translated into new therapies, the researchers will employ a combination of bioinformatics, protein production and high-end biophysical and structural biology techniques. The collected information will ultimately be combined in an information pipeline for both research and biotechnology.
Project title: "NMR Spin Relaxation to probe Side-Chain Dynamics in IDPs" (P35098)
Liquid-liquid Phase Separation in Biology – Ellipse, funded by the Austrian Science Fund FWF.
Project title: Computergestützte Strukturbiologie