Interfakultäres Institut für Mikrobiologie und Infektionsmedizin

Arbeitsgruppe Kronenberger

Thales Kronenberger

Tel.: +49 7071 29 - 81526
E-mail: thales.kronenbergerspam prevention@uni-tuebingen.de
Research Gate Profile

Lebenslauf

Thales Kronenberger studied Biology in São Paulo (Brazil) and obtained his MSc (2014) and PhD (2017) at the University of São Paulo in the field of Pathogen/Host interactions and infection biology, including a visiting scientist period at Fraunhofer ScreeningPort (Hamburg) working with High-Throughput Screening assay development. He held a postdoctoral position at the University of Tübingen (2017-2024) initially at the medical faculty and later in the Pharmacy Department. Altogether for a period of six-year combined period, applying different molecular modelling approaches, ranging from identifying primary hits using virtual screening and employing molecular dynamics simulations to generate reliable protein-ligand interaction models. He has a consultant role on computational chemistry at the Molab AI company (München), providing guidance and support on the development of combined biophysical methods with machine learning strategies. Since 2023, he holds the title of Dozent in molecular modelling from the University of Eastern Finland (Kuopio) and currently works as a Junior Group leader in the Medical Microbiology.

Research Focus

We believe that static descriptions of the protein structures are not sufficient to describe its dynamic system. Proteins display different conformations when in association with others, as multimers or heterocomplexes than when they are alone as monomers. However, we realized that most of the current simulations rely on monomeric structures, mostly due to limitations on computational resources. Since, small molecules of interest could differentially bind in unique protein conformations, we often do not have a single structure to start understanding this problem. Our group focus on generating biologically relevant models to explain protein-ligand interactions and help to develop novel inhibitors.

Our approach allowed us to answer the question of whether multimerization can contribute to large conformational changes influence the protein-drug interactions. By simulating multiple crystal structures and models with and without binding partners and systematically comparing them in terms of movement and changes in the interface. We identified which components are not only relevant for dimerization/multimerization, but that offer opportunities for future site-direct mutagenesis, as a target validation, development of inhibitors for novel binding site otherwise not present in the monomeric structures, and most importantly protein-protein interaction inhibitors development.

Ausgewählte Publikationen

  1. Rashidian A*, Dusek J*, Drastik M, Smutná L, Fritsche K, Braeuning A, Honkakoski P, Poso A, Kronenberger T#, Pavek P#. (2024) Filling the blank space: Filling the blank space: Branched 4-nonylphenols isomers are responsible for robust constitutive 1 androstane receptor (CAR) activation by nonylphenol. Environ Sci Technol. 58(16):6913-6923. doi: 10.1021/acs.est.3c10096.
  2. Kronenberger T*, Laufer S, Pillaiyar T*#. (2023) COVID-19 therapeutics: small molecule drugs development targeting SARS-CoV-2 main protease. Drug Disc Today. 28(6):103579. doi: 10.1016/j.drudis.2023.103579.
  3. Tonduru AK, Adla SK, Huttunen KM, Kronenberger T#, Poso A#. (2022) Comparative modelling of OATPs with structural insights and comparison of binding modes. Molecules. 27(23):8531. doi: 10.3390/molecules27238531.
  4. Díaz-Holguín A*, Rashidian A*, Pijnenburg D, Ferreira GM, Stefela A, Kaspar M, Kudova E, Poso A, van Beuningen R, Pavek P, Kronenberger T#. (2022) When the two become one, conformational changes in FXR/RXR heterodimers bound to steroidal antagonists. Chem Med Chem. e202200556. doi: 10.1002/cmdc.202200556.
  5. Maltarollo VG, Shevchenko E, Lima I, Cino EA, Ferreira GM, Poso A, Kronenberger T#. (2022) Do go chasing waterfalls: enoyl reductase (FabI) in complex with inhibitors stabilize tetrameric structure and opens water channels. J Chem Inf Model. 62(22):5746-5761. doi: 10.1021/acs.jcim.2c01178.
  6. Ferreira GM, Pillaiyar T, Hirata MH, Poso A, Kronenberger T#. (2022) SARS-CoV-2 papain-like protease: Conformational changes in BL2’ regions induced by PLpro inhibitors. Sci Rep. 12(1):11585. doi: 10.1038/s41598-022-15181-y.