Otto Loewi
“A drug is a substance which, if injected into a rabbit, produces a paper.”
Otto Loewi was a German-born pharmacologist and psychobiologist who discovered the role of acetylcholine as the body’s neurotransmitter. He was awarded the Nobel Prize in Physiology or Medicine in 1936 for his discovery. Although his statement was simplistic and exaggerated, the essence of the message was correct and indicative of recent decades. However, in addition to the ethical complications, it has become apparent in the last 100 years that animal experiments are not sufficiently and comprehensively suited to be a model for the human organism.
Combining next-generation bioinformatics with high-performance computing techniques and deep learning enables a deeper understanding of biological processes and contributes to future drug and protein research pipelines.
Catapulting knowledge of protein dynamics and interactions to the next level is, therefore, the greatest challenge and rewarding motivation. The methods and data obtained enable new approaches, e.g. for understanding signal transduction, membrane transport, electron transfer systems, cell metabolism, apoptosis or muscle contractions in healthy and diseased states. Further applications are not limited to the human organism and allow the study of bacteria, archaea, plants or even synthetic biomolecular interactions within and between species that help to understand allergies, develop new antibiotics, design the next series of synthetic organisms or finally even replace animal experiments by running virtual clinical trials.
35 peer-reviewed publications · h-index 25 · 2,290 citations
2025
Steinkellner, G., Kroutil, W., Gruber, K. & Gruber, C.C.*
AlphaFold 3 is great — but it still needs human help to get chemistry right.
Nature 637, 548 (Correspondence, 2025).
DOI: 10.1038/d41586-025-00111-5
Riegler-Berket, L. et al. (incl. Gruber, C.C.)
M. tuberculosis meets European Lead Factory — Identification and structural characterization of novel Rv0183 inhibitors.
Disease and Therapeutics 1, 100002 (2025).
DOI: 10.1016/j.dist.2025.100002 
2024
Simic, S., Cespugli, M., Hetmann, M.C. et al. (incl. Gruber, C.C.)
Cavity-Based Discovery of New Fatty Acid Photodecarboxylases.
ChemBioChem 25(24), e202400631 (2024).
DOI: 10.1002/cbic.202400631
Parigger, L., Krassnigg, A., Hetmann, M. et al., Gruber, K., Steinkellner, G. & Gruber, C.C.*
CavitOmiX Drug Discovery: Engineering Antivirals with Enhanced Spectrum and Reduced Side Effects for Arboviral Diseases.
Viruses 16, 1186 (2024).
DOI: 10.3390/v16081186
Hetmann, M., Parigger, L. et al., Gruber, K., Steinkellner, G., Ruau, D. & Gruber, C.C.*
Folding the human proteome using BioNeMo: A fused dataset of structural models for machine learning purposes.
Scientific Data 11, 591 (2024).
DOI: 10.1038/s41597-024-03403-z
Schimunek, J. et al. (incl. Gruber, C.C.; 148 authors)
A community effort in SARS-CoV-2 drug discovery.
Molecular Informatics 43(1), e202300262 (2024).
DOI: 10.1002/minf.202300262
2023
Braun, M., Gruber, C.C.*, Krassnigg, A. et al.
Accelerating Biocatalysis Discovery with Machine Learning: A Paradigm Shift in Enzyme Engineering, Discovery, and Design.
ACS Catalysis 13(21), 14454–14469 (2023).
DOI: 10.1021/acscatal.3c03417
Parigger, L. et al., Gruber, K., Steinkellner, G. & Gruber, C.C.*
AI-assisted structural consensus-proteome prediction of human monkeypox viruses.
Microbiology Spectrum 11, e02315-23 (2023).
DOI: 10.1128/spectrum.02315-23
Hetmann, M. et al., Gruber, K., Steinkellner, G. & Gruber, C.C.*
Identification and validation of fusidic acid and flufenamic acid as inhibitors of SARS-CoV-2 replication using DrugSolver CavitomiX.
Scientific Reports 13, 11783 (2023).
DOI: 10.1038/s41598-023-39071-z
Köchl, K. et al., Gruber, K., Steinkellner, G. & Gruber, C.C.*
Optimizing variant-specific therapeutic SARS-CoV-2 decoys using deep-learning-guided molecular dynamics simulations.
Scientific Reports 13, 774 (2023).
DOI: 10.1038/s41598-023-27636-x
2022
Parigger, L. et al., Gruber, K., Steinkellner, G. & Gruber, C.C.*
Recent changes in the mutational dynamics of the SARS-CoV-2 main protease substantiate the danger of emerging resistance to antiviral drugs.
Frontiers in Medicine 9, 1061142 (2022).
DOI: 10.3389/fmed.2022.1061142
Structural bioinformatics analysis of SARS-CoV-2 variants reveals higher hACE2 receptor binding affinity for Omicron B.1.1.529 spike RBD compared to wild type reference
Vedat Durmaz, Katharina Köchl, Andreas Krassnigg, Lena Parigger, Michael Hetmann, Amit Singh, Daniel Nutz, Alexander Korsunsky, Ursula Kahler, Centina König, Lee Chang, Marius Krebs, Riccardo Bassetto, Tea Pavkov-Keller, Verena Resch, Karl Gruber, Georg Steinkellner & Christian C. Gruber
Sci Rep 12, 14534 (2022)
nature.com/articles/s41598-022-18507-y
M. Prattes, I. Grishkovskaya, V.V. Hodirnau, I. Rössler, I. Klein, C. Hetzmannseder, G. Zisser, C.C. Gruber, K. Gruber, D. Haselbach & H. Bergler
Structural basis for inhibition of the AAA-ATPase Drg1 by diazaborine.
Nature Communications 12, 3483 (2021)
nature.com/articles/s41467-021-23854-x
Singh, A., Steinkellner, G., Köchl, K., Gruber, K. & Gruber, C. C.*
Serine 477 plays a crucial role in the interaction of the SARS-CoV-2 spike protein with the human receptor ACE2.
Sci Rep 11, 4320 (2021).
nature.com/articles/s41598-021-83761-5
My milestone on a genome wide level in 2021. My contribution to this consortial work was to establish the dynamic structural viral proteome and to identify potential binding sites in 17 target proteins.
Gorgulla, C. et al.
A multi-pronged approach targeting SARS-CoV-2 proteins using ultra-large virtual screening.
iScience 24, 102021 (2021).
cell.com/iscience/fulltext/S2589-0042(20)31218-9
2016
Aschauer, P., Rengachari, S., Lichtenegger, J., Schittmayer, M., Das, K.M.P., Mayer, N., Breinbauer, R., Birner-Gruenberger, R., Gruber, C.C., Sachs, G., Streith, I. & Oberer, M.
Crystal structure of the Saccharomyces cerevisiae monoglyceride lipase Yju3p.
Biochimica et Biophysica Acta (BBA) – Molecular and Cell Biology of Lipids 1861 (9), 1304–1311 (2016).
DOI: 10.1016/j.bbalip.2016.02.005
2014
Łyskowski, A., Gruber, C., Steinkellner, G., Schürmann, M., Schwab, H., Gruber, K. & Steiner, K.
Crystal structure of an (R)-selective ω-transaminase from Aspergillus terreus.
PLoS ONE 9 (1), e87350 (2014).
DOI: 10.1371/journal.pone.0087350
The proof-of-principle of the Catalophore technology and basis of the foundation of the company Innophore. I planned, executed and analysed the bioinformatics data mining experiments (*equal contribution).
Steinkellner, G.* & Gruber C.C.* et al.
Identification of promiscuous ene-reductase activity by mining structural databases using active site constellations.
Nature communications 5, 1–9 (2014)
nature.com/articles/ncomms5150
2013
Ribitsch, D., Yebra, A.O., Zitzenbacher, S., Wu, J., Nowitsch, S., Steinkellner, G., Greimel, K., Dolber, A., Boccone, M., Lishi, H., Herrero Acero, E., Kauffmann, H., Gross, H., Brandstadt, K., Gruber, C.C., Berg, G., Guebitz, G.M. & Schwab, H.
Fusion of binding domains to Thermobifida cellulosilytica cutinase to tune sorption characteristics and enhancing PET hydrolysis.
Biomacromolecules 14 (6), 1769–1776 (2013).
Goessweiner-Mohr, N., Grumet, L., Arends, K., Pavkov-Keller, T., Gruber, C.C., Gruber, K., Zehetmayer, S., Zangger, K. & Keller, W.
The 2.5 Å structure of the enterococcus conjugation protein TraM resembles VirB8 type IV secretion proteins.
Journal of Biological Chemistry 288 (3), 2018–2028 (2013).
2012
Gruber, C.C. & Pleiss, J.
Molecular modeling of lipase binding to a substrate–water interface.
Lipases and Phospholipases: Methods and Protocols, 313–327 (2012).
DOI: 10.1007/978-1-61779-600-5_19
As senior scientist, I used molecular dynamics for various protein and protein-interface systems. In these exemplary publications and contributed the bioinformatics simulations, refinements and analysis.
Rengachari, S. et al.
The structure of monoacylglycerol lipase from Bacillus sp. H257 reveals unexpected conservation of the cap architecture between bacterial and human enzymes.
Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids 1821, 1012–1021 (2012). (Gruber, C. C., 4th author)
pubmed.ncbi.nlm.nih.gov/22561231/
Ferrario, V. et al.
Elucidating the structural and conformational factors responsible for the activity and substrate specificity of alkanesulfonate monooxygenase.
Journal of Biomolecular Structure and Dynamics 30, 74–88 (2012). (Gruber, C. C. , 4th author)
pubmed.ncbi.nlm.nih.gov/22571434/
Gruber, C. C. & Pleiss, J.
Systematic benchmarking of large molecular dynamics simulations employing GROMACS on massive multiprocessing facilities.
Journal of computational chemistry 32, 600–606 (2011).
onlinelibrary.wiley.com/doi/abs/10.1002/jcc.21645
Gruber, C. C. & Pleiss, J.
Lipase B from Candida antarctica binds to hydrophobic substrate–water interfaces via hydrophobic anchors surrounding the active site entrance.
Journal of Molecular Catalysis B: Enzymatic 84, 48–54 (2012)
sciencedirect.com/science/article/abs/pii/S1381117712001348
2010
Voss, C.V., Gruber, C.C. & Kroutil, W.
Deracemisation of secondary alcohols via biocatalytic stereoinversion.
Synlett 2010 (07), 991–998 (2010).
2009
Bodlenner, A., Glueck, S.M., Nestl, B.M., Gruber, C.C., Baudendistel, N., Hauer, B., Kroutil, W. & Faber, K.
Biocatalytic racemization of α-hydroxycarboxylic acids using a stereo-complementary pair of α-hydroxycarboxylic acid dehydrogenases.
Tetrahedron 65 (36), 7752–7755 (2009).
DOI: 10.1016/j.tet.2009.06.051
2008
Voss, C.V., Gruber, C.C. & Kroutil, W.
Deracemization of secondary alcohols through a concurrent tandem biocatalytic oxidation and reduction.
Angewandte Chemie International Edition 47 (4), 741–745 (2008).
Gruber, C. C. et al.
An algorithm for the deconvolution of mass spectrosopic patterns in isotope labeling studies. Evaluation for the hydrogen− deuterium exchange reaction in ketones.
The Journal of organic chemistry 72, 5778–5783 (2007)
pubs.acs.org/doi/10.1021/jo070831o
Voss, C. V. & Gruber, C. C. et al.
Orchestration of concurrent oxidation and reduction cycles for stereoinversion and deracemisation of sec-alcohols.
Journal of the American Chemical Society 130, 13969–13972 (2008)
pubs.acs.org/doi/10.1021/ja804816a
Gruber, C. C. et al.
Emulation of racemase activity by employing a pair of stereocomplementary biocatalysts.
Chemistry–A European Journal 13, 8271–8276 (2007)
chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.200700528
2007
Voss, C.V., Gruber, C.C. & Kroutil, W.
A biocatalytic one-pot oxidation/reduction sequence for the deracemisation of a sec-alcohol.
Tetrahedron: Asymmetry 18 (2), 276–281 (2007).
DOI: 10.1016/j.tetasy.2007.01.013
2006
Gruber, C.C., Lavandera, I., Faber, K. & Kroutil, W.
From a racemate to a single enantiomer: deracemization by stereoinversion.
Advanced Synthesis & Catalysis 348 (14), 1789–1805 (2006).
Edegger, K., Gruber, C.C., Poessl, T.M., Wallner, S.R., Lavandera, I., Faber, K., Niehaus, F., Eck, J., Cerber, R., Kroutil, W. & Ebert, C.
Biocatalytic deuterium- and hydrogen-transfer using over-expressed ADH-‘A’: enhanced stereoselectivity and 2H-labeled chiral alcohols.
Chemical Communications, 2402–2404 (2006).
Edegger, K., Gruber, C.C., Faber, K., Hafner, A. & Kroutil, W.
Optimization of Reaction Parameters and Cultivation Conditions for Biocatalytic Hydrogen Transfer Employing Overexpressed ADH-‘A’ from Rhodococcus ruber DSM 44541.
Engineering in Life Sciences 6 (2), 149–154 (2006).
2005
Poessl, T.M., Kosjek, B., Ellmer, U., Gruber, C.C., Edegger, K., Faber, K., Hildebrandt, P., Bornscheuer, U.T. & Kroutil, W.
Non-Racemic Halohydrins via Biocatalytic Hydrogen-Transfer Reduction of Halo-Ketones and One-Pot Cascade Reaction to Enantiopure Epoxides.
Advanced Synthesis & Catalysis 347 (14), 1827–1834 (2005).
Click here for a full list of publications in Google scholar
Five patents (3 granted, 2 pending)
Thermostable Ancestral Imine Reductases for Robust and Scalable Imine Reduction/Reductive Amination Reactions
Invention disclosure filed (Innophore GmbH / RWTH Aachen, 2026). Patent pending.
Performance-enhanced protease variants
Published 2026, Filed 2023. US20260043015A1. Assignee: Henkel AG and Co KGaA.
patents.google.com/patent/US20260043015A1/en
Determining novel enzymatic functionalities using three-dimensional point clouds representing physico chemical properties of protein cavities
Filed 2013, Granted 2020. US20150302142A1 / EP2923291A1 / WO2014080005A.
patents.google.com/patent/US20150302142A1/en
Process for the enzymatic deracemization of secondary alcohols
Granted 2012. EP2257635B1.
patents.google.com/patent/EP2257635B1/en
Process for the racemization of optically active secondary alcohols with the use of two alcohol dehydrogenases
Granted 2010. US7795004B2.
patents.google.com/patent/US7795004B2/en
Invited Articles, Research Highlights & Other Publications
2024
NVIDIA
Innophore Accelerates Drug Discovery with NVIDIA AI and AWS.
NVIDIA Case Study (2024).
nvidia.com/en-us/case-studies/innophore-ai-drug-discovery
2023
Gruber, C.C.
Vulkanland — A Garden Railway that Connects Stories and Generations of a Family.
Spur G Magazin 31, 20–25 (2023).
One of the publications I am most proud of — an article in the renowned LGB Spur G Magazin about the garden railway I built with my son. What started with a few second-hand tracks and a locomotive grew into “Vulkanland”: a G-scale layout in the heart of Styria with 11 locomotives on four independent circuits, a glowing volcano, a Golden Gate Bridge, and a Statue of Liberty. It is a playground of imagination where learning and play go hand in hand — and proof that the best engineering projects are the ones you build with your family.
2022
Gruber, C.C., Singh, A. & Resch, V.
Discovering dominant viral variants and their implications for host-protein binding.
Nature Research Communities (Research Highlight, 2022).
communities.springernature.com
Gruber, C.C., Kochl, K., Krassnigg, A., Schopper, T. & Resch, V.
Deceiving viruses: a blueprint for fighting future outbreaks and pandemics?
Nature Research Communities (Research Highlight, 2022).
communities.springernature.com
Resch, V. & Gruber, C.C.
Innophore’s 3D point clouds provide a head start in monitoring emerging SARS-CoV-2 variants.
Invited article, Nature Health Blog (2022).
go.nature.com/3NebrBk
2021
Amazon Web Services
Evaluating SARS-CoV-2 binding affinities using Yasara simulations on AWS.
AWS for Industries Blog (2021).
aws.amazon.com/blogs/industries
Funding and support was kindly provided by the following
agencies, institutions and companies
Public Funding Agencies
FFG – Österreichische Forschungsförderungsgesellschaft · FWF – Der Wissenschaftsfonds · DFG – Deutsche Forschungsgemeinschaft · SFG – Steirische Wirtschaftsförderung · EU FP7 & Horizon 2020
Industry
Innophore · EOSS Industries · NVIDIA · Amazon Web Services (AWS) · Google · Henkel · Roche · Takeda · Moderna · Novartis
Academic Institutions
University of Graz · University of Stuttgart · SimTech Cluster of Excellence · acib – Austrian Centre of Industrial Biotechnology