The Faculties

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The Heinrich Heine University (HHU) is divided up into five faculties which are all located on one campus. The oldest one and core of the university is the Faculty of Medicine, followed by the Faculty of Mathematics and Natural Sciences and the Faculty of Arts and Humanities. In the late 1980s and early 1990s the Faculty of Business and Economics and the Faculty of Law were then launched.

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    Acoustics of word-final S
    (Heinrich-Heine-Universität Düsseldorf, 2019-03-19) Plag, Ingo; Homann, Julia; Kunter, Gero
    Recent research has shown that homophonous lexemes show systematic phonetic differences (e.g. Gahl 2008, Drager 2011), with important consequences for models of speech production such as Levelt et al. (1999). These findings also pose the question of whether similar differences hold for allegedly homophonous affixes (instead of free lexemes). Earlier experimental research found some evidence that morphemic and nonmorphemic sounds may differ acoustically (Walsh & Parker 1983, Losiewicz 1992). This paper investigates this question by analyzing the phonetic realization of non-morphemic /s/ and /z/, and of six different English /s/ and /z/ morphemes (plural, genitive, genitive-plural and 3rd person singular, as well as cliticized forms of has and is). The analysis is based on more than 600 tokens extracted from conversational speech (Buckeye Corpus, Pitt et al. 2007). Two important results emerge. First, there are significant differences in acoustic duration between some morphemic /s/’s and /z/’s and non-morphemic /s/ and /z/, respectively. Second, there are significant differences in duration between some of the morphemes. These findings challenge standard assumptions in morphological theory, lexical phonology and models of speech production.
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    Anomalous phylogenetic behavior of ribosomal proteins in metagenome assembled asgard archaea
    (Genome Biology and Evolution, 2020) Garg, SG; Kapust, N; Lin, W; Knopp, M; Tria, FDK; Nelson-Sathi, S; Gould, SB; Fan, L; Zhu, R; Zhang, C; Martin, WF
    Supplement to a paper in GBE (title: Anomalous phylogenetic behavior of ribosomal proteins in metagenome assembled asgard archaea)
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    Chaperone/ETR1 Structural Models for: Molecular Mechanism and Structural Models of Protein-Mediated Copper Transfer to the Arabidopsis thaliana Ethylene Receptor ETR1 at the ER Membrane
    (N/A, 2025) Dluhosch, Dominik; Kersten, Lisa Sophie; Minges, Alexander; Schott-Verdugo, Stephan; Gohlke, Holger; Groth, Georg
    In plants, the gaseous plant hormone ethylene regulates a wide range of developmental processes and stress responses. The small unsaturated hydrocarbon is detected by a family of receptors (ETRs) located in the membrane of the endoplasmic reticulum, which rely on a monovalent copper cofactor to detect this hydrocarbon. The copper-transporting P-type ATPase RAN1 (HMA7), located in the same membrane, is known to be essential for the biogenesis of ETRs. Still, the precise molecular mechanism by which the receptors acquire their copper cofactor remains unclear. A recent study by our laboratory demonstrated a direct interaction between RAN1 and soluble copper chaperones of the ATX1 family with the model ethylene receptor ETR1, providing initial insights into the mechanism by which copper is transferred from the cytosol to the membrane-bound receptors. In this study, we further investigated these interactions with respect to the function of individual domains in complex formation. To this end, we combined biochemical experiments and computational predictions and unraveled the processes and mechanisms by which copper is transferred to ETR1 at the molecular level.
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    Data for "Early-stage autophagy inhibitors targeting the ATG101-ATG13 subunit of the ULK1 complex"
    (2025) Mudrovcic, Korana; Gopalswamy, Mohanraj; Gohlke, Holger
    Autophagy is commonly up- or down-regulated in cancer cells due to the unique metabolic needs of these cells, and small molecules modulating the autophagy pathway are already in clinical trials. However, specific autophagy-targeting compounds remain rare. A new potential mechanism for effective early-stage autophagy inhibition was described by us and others recently, involving the inhibition of the interaction between ATG101 and ATG13 subunits of the autophagy-initiating ULK1 complex. Here, we describe the discovery of two small molecules inhibiting the ATG101-ATG13 interaction, one by binding to ATG101 with micromolar affinity (EC50 = 151 µM) and the other by binding to both ATG101 and ATG13 with micromolar affinity (EC50 = 135 µM and EC50 = 107 µM, respectively). In two independent assays, both compounds inhibit autophagy. Scrutinizing the binding mechanism by molecular dynamics simulations and STD-NMR spectroscopy indicates that the compounds bind to ATG101 in an orthosteric fashion, at the interface of the protein-protein interaction, while the binding to ATG13 is allosteric. Both compounds have a favorable predicted ADME-Tox profile. The compounds can serve as tool compounds to inhibit autophagy or as candidates for further optimization toward lead structures.
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    Data for "Evidence for Epibatidine Binding to the Desensitization Gate in α7 nAChR from Molecular Dynamics Simulations and Cryo-EM"
    (N/A, 2025) Kaiser, Jesko; Gertzen, Christoph; Mann, Daniel; Sachse, Carsten; Gohlke, Holger
    The homopentameric α7 nicotinic acetylcholine receptor (nAChR) is a ligand-gated ion channel widely expressed in the human nervous system and susceptible to regulation via allosteric modulators. A recent cryo-EM map of the receptor (EMD 22983) in the presence of (±)-epibatidine revealed the presence of several Coulomb density regions that did not contain an atomic model (PDB ID: 7KOX). We conducted unbiased molecular dynamics simulations of free ligand diffusion of the components of experimental buffers utilized to obtain the cryo-EM structure in the presence of α7-nAChR. In addition to the previously documented binding of epibatidine to the orthosteric site and Ca2+ between E44 and E172, the simulations indicated that epibatidine can also bind within the pore of α7-nAChR. This finding is consistent with the unmodeled Coulomb density observed in the region of the desensitization gate. The data presented here suggests that nAChR ligands characterized as orthosteric binders may bind to additional sites within the receptor and expands the receptor’s pocketome.
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    Data for "Identification of autophagy inhibitors selectively targeting the ATG13-ATG101 protein-protein interaction"
    (2025) Mudrovcic, Korana; Gopalswamy, Mohanraj; Gohlke, Holger
    The dysregulation of autophagy promotes the development of several diseases like such as neurodegeneration, infection, or cancer. To keep up with their metabolic demand under low nutrient and/or oxygen conditions typically present in the tumor microenvironment, cancer cells can upregulate autophagy autonomously or in surrounding cells. Therefore, the inhibition of autophagy is desired in these settings. However, to date, drugs targeting autophagy selectively remain rare. The autophagy-inducing ULK1 complex comprises ULK1/2, FIP200, and a heterodimer consisting of ATG13 and ATG101. We previously showed that the ATG13-ATG101 protein-protein interaction is crucial for the assembly of the ULK1 complex and initiation of autophagic activity. Thus, targeting the ATG13-ATG101 protein-protein interaction with small molecules promises to yield new tools for the study of autophagy as well as to deliver new therapeutic starting points. By screening a diversity set of 15k compounds in a biochemical setup, followed by extensive cell-based validation studies, we identified the compounds AFS30 and AFS32. Both compounds inhibited the ATG13-ATG101 PPI in the low micromolar range and led to reduced autophagic activity in different cell lines, with IC50 values of 3-4 µM in the LC3 HiBiT reporter assay. Spectral shift assays, molecular dynamics simulations, and STD-NMR suggested that the compounds bind allosterically to ATG13. AFS30 and AFS32 also promoted apoptosis in different cancer cell lines exposed to nutrient stress. We propose that AFS30 and AFS32 are promising lead compounds for the development of PPI inhibitors that selectively inhibiting the ATG13-ATG101 interaction and thus autophagy.
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    Data for "Influence of ionic liquids on enzymatic asymmetric carboligations"
    (N/A, 2025) El Harrar, Till; Gohlke, Holger
    The asymmetric mixed carboligation of aldehydes catalyzed by thiamine diphosphate (ThDP)-dependent enzymes provides a sensitive system for monitoring changes in activity, chemo-, and enantioselectivity. While previous studies have shown that organic cosolvents influence these parameters, we now demonstrate that similar effects occur upon addition of water-miscible ionic liquids (ILs). In this study, six ThDP-dependent enzymes were analyzed in the presence of 14 ILs under comparable conditions to assess their influence on enzymatic carboligation reactions yielding 2-hydroxy ketones. ILs exerted a moderate to strong influence on activity and, more notably, altered enantioselectivity. (R)-selective reactions were generally stable upon IL addition, while (S)-selective reactions frequently showed reduced selectivity or even inversion to the (R)-enantiomer. The most significant change was observed for the ApPDC_E469G variant of pyruvate decarboxylase from Acetobacter pasteurianus, where the enantiomeric excess shifted from 86% (S) to 60% (R) in the presence of 9% (w/v) Ammoeng 102. Control experiments indicated that this shift was primarily due to the Ammoeng cation rather than the anion. To explore the molecular basis of this phenomenon, all-atom molecular dynamics (MD) simulations were performed on wild-type ApPDC and the E469G variant in Ammoeng 101 and Ammoeng 102. The simulations revealed that hydrophobic and hydrophilic regions of the Ammoeng cations interact with the (S)-selective binding pocket, thereby favoring formation of the (R)-product. These results highlight the potential of solvent engineering for modulating enzyme selectivity and demonstrate that MD simulations can capture functionally relevant enzyme–solvent interactions at the atomic level.
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    Data for "Mechanistic Insights into the Structural Asymmetry of the LanFEG Transporter NisFEG in Lantibiotic Immunity"
    (2025) Cea, Pablo; Gohlke, Holger
    Nisin is one of the best studied antimicrobial peptides. Still, how nisin-producing strains can protect themselves against nisin’s bactericidal effects is only partially understood. Located within the nisin biosynthesis operon, the heterotetrameric ABC transporter NisFEG transports nisin to the extracellular environment, granting autoimmunity to the producer strain. NisFEG belongs to the LanFEG family of ABC transporters, members of which are found in some lantibiotic-producing bacterial strains. However, their structure has not been elucidated. In this work, we constructed a full atom model of NisFEG in the ATP-bound conformation. The architecture of the complex reveals a narrow transmembrane interface with prominent lateral clefts, similar to those observed in other exporters of hydrophobic compounds. Through molecular dynamics (MD) simulations, we observed that one of the most conserved elements of the LanFEG family, the E-loop of the nucleotide binding domain, interacts preferentially with a small intracellular helix of the NisG transmembrane chain. Cosolvent MD simulations reveal the presence of a putative binding site within the lateral cleft of the transporter, next to the transmembrane chain NisE. Mutational analysis showed that large hydrophobic residues near this putative site are relevant to the transporter function, and more so than analogous residues in the opposite cleft. Our results suggest that nisin extrusion operates in an asymmetric manner, where contacts between the E-loop and NisG are the driving force for the conformational changes triggered by ATP hydrolysis, whereas the NisE subunit is the main mediator of interactions with the lantibiotic. This functional asymmetry could provide an explanation for why the LanFEG family has evolved two distinct transmembrane chains, where each one was selected to perform a single step in an optimal way, maximizing the immunity of lantibiotic-producing bacteria.
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    Data for "Molecular Insights into CLD Domain Dynamics and Toxin Recruitment of the HlyA E. coli T1SS"
    (N/A, 2025) Gentile, Rocco; Schott-Verdugo, Stephan; Khosa, Sakshi; Bonus, Michele; Reiners, Jens; Smits, Sander H.J.; Schmitt, Lutz; Gohlke, Holger
    Escherichia coli is a Gram-negative opportunistic pathogen causing nosocomial infections through the production of various virulence factors. Type 1 secretion systems (T1SS) contribute to virulence by mediating one-step secretion of unfolded substrates directly into the extracellular space, bypassing the periplasm. A well-studied example is the hemolysin A (HlyA) system, which secretes the HlyA toxin in an unfolded state across the inner and outer membranes. T1SS typically comprise a homodimeric ABC transporter (HlyB), a membrane fusion protein (HlyD), and the outer membrane protein TolC. Some ABC transporters in T1SS also contain N-terminal C39 peptidase or peptidase-like (CLD) domains implicated in substrate interaction. Recent cryo-EM studies have resolved the inner-membrane complex as a trimer of HlyB homodimers with associated HlyD protomers. However, a full structural model including TolC remains unavailable. We present the first complete structural model of the HlyA T1SS, constructed using template- and MSA-based information and validated by SAXS. Molecular dynamics simulations provide insights into the function of the CLD domains, which are partially absent from existing cryo-EM structures. These domains may modulate transport by stabilizing specific conformations of the complex. Simulations with a C-terminal fragment of HlyA indicate that toxin binding occurs in the occluded conformation of HlyB, potentially initiating substrate transport through a single HlyB protomer before transitioning to an inward-facing state. HlyA binding also induces allosteric effects on HlyD, altering key residues involved in TolC recruitment. These results indicate how substrate recognition and transport are coupled and may support the development of antimicrobial strategies targeting the T1SS.
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    Data for "Sulfated glycosaminoglycans inhibit Arenavirus entry and modulate anti-viral immunity and pathology"
    (N/A, 2025) Rähse, Nick; Lapsien, Marco; Gohlke, Holger
    Viral infections pose significant challenge due to limited availability and efficacy of treatments. Current therapies primarily inhibit viral replication, but are often virus-specific and may lead to drug resistance. Sulfated glycosaminoglycans (GAGs) emerged as promising candidates for antiviral therapy, preventing viral binding to host cells and inhibiting cell entry, offering a novel therapeutic strategy targeting broad range of viruses, addressing the limitations of existing antiviral drugs. Here, we demonstrate highly-sulfated GAGs are able to limit infectivity of different pathogenic and non-pathogenic Arenaviruses. In an in vivo model setting, dextran sulfate administered during the acute phase of LCMV infection reduced viral load in organs and decreased liver pathology, which was associated with improved effector T cell functions. In turn, exposure of LCMV towards dextran sulfate at the beginning of infection caused limited immune activation, resulting in reduced T cell immunity, prolonged infection and increased immunopathology. These findings indicate the potential use of GAGs against Arenavirus infections and highlight that timing of therapeutic regimens might be critical for clinical efficacy.
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    Data for "TopEC: Improved classification of enzyme function by a localized 3D protein descriptor and 3D Graph Neural Networks"
    (N/A, 2024-08-25) van der Weg, Karel; Merdivan, Erinc; Piraud, Marie; Gohlke, Holger
    Accurately annotating molecular function of enzymes remains challenging. Computational methods can aid in this and allow for high-throughput annotation. Tools available for inferring enzyme function from general sequence, fold, or evolutionary information are generally successful. However, they can lead to misclassification if for certain sequences a deviation in local structural features influences the function. Here, we present TopEC, a 3D graph neural network based on a localized 3D descriptor to learn chemical reactions of enzymes from (predicted) enzyme structures and predict Enzyme Commission (EC) classes. Using the message passing frameworks from SchNet and DimeNet++, we include distance and angle information to improve the predictive performance compared to regular 2D graph neural networks. We obtained significantly improved EC classification prediction (F-score: 0.72) to 2D GNNs, without fold bias at residue and atomic resolutions and trained networks that can classify both experimental and computationally generated enzyme structures for a vast functional space (> 800 ECs). Our model is robust to uncertainties in binding site locations and similar functions in distinct binding sites. By investigating the importance of each graph node to the predictive performance, we see that TopEC networks learn from an interplay between biochemical features and local shape-dependent features. TopEC is available as a repository, including accompanying data, on github: https://github.com/IBG4-CBCLab/TopEC. The data in this repository is available under the CC-BY-NC-SA 4.0 license.
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    Downloads for Pipeline "PlugNSeq: An Easy, Rapid, and Streamlined mRNA-Seq Data Analysis Pipeline Empowering Insightful Exploration with Well-Annotated Organisms, Requiring Minimal Bioinformatic Expertise"
    (Protocols.io, 2025-05-26) Mai, Hans-Jörg
    Here, we provide the required folder structure for the PlugNSeq mRNA-Seq data analysis pipeline. It contains ZIP-compressed archives (*.zip) for Windows, and tarballs (*.tar.gz) for Linux and Mac OS.
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    Electronic Supporting Information for MOLSTRUC-D-21-03929
    (Journal of Molecular Structure, 2021) Hebestreit, Marie-Luise
    This collection gives a) the experimental and simulated zero-field spectrum of the electronic origin of 6-methylindole b) the experimental and simulated Stark spectrum of the electronic origin of 6-methylindole at 425.49 V/cm
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    Example input data for FCFit
    (No, 2022) Michael, Schmitt
    Collection of example input data for FCFit
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    FC-Fit
    (No, 2022) Krügler, Daniel; Schmitt, Michael
    FCfit is program for the simulation and fit of vibronic absorption and emission spectra based on the evaluation of relative Franck-Condon (FC) factors and/or Franck-Condon-Herzberg-Teller (FCHT) theory. The program computes the FC integrals of multidimensional, harmonic oscillators mainly based on the recursion formula given in the papers of Doktorov, Malkin, and Man’ko.
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    Ferredoxin reduction by hydrogen with iron functions as an evolutionary precursor of flavin-based electron bifurcation
    (Institute of Molecular Evolution, 2023) Brabender, Max; Henriques Pereira, Delfina P.; Mrnjavac, Natalia; Schlikker, Manon Laura; Kimura, Zen-Ichiro; Sucharitakul, Jeerus; Kleinermanns, Karl; Tüysüz, Harun; Buckel, Wolfgang; Preiner, Martina; Martin, William F.
    Raw data of UV-VIS spectra
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    Functional and structural characterization of interactions between opposite subunits in HCN pacemaker channels
    (N/A, 2021-08-05) Kondapuram, Mahesh; Frieg, Benedikt; Yüksel, Sezin; Schwabe, Tina; Sattler, Christian; Lelle, Marco; Schweinitz, Andrea; Schmauder, Ralf; Benndorf, Klaus; Gohlke, Holger; Kusch, Jana
    Hyperpolarization-activated and cyclic nucleotide (HCN) modulated channels are tetrameric cation channels. In each of the four subunits, the intracellular cyclic nucleotide-binding domain (CNBD) is coupled to the transmembrane domain via a helical structure, the C-linker. High-resolution channel structures suggest that the C-linker enables functionally relevant interactions with the opposite subunit, which might be critical for coupling the conformational changes in the CNBD to the channel pore. We combined mutagenesis, patch-clamp technique, confocal patch-clamp fluorometry, and molecular dynamics simulations to show that residue K464 of the C-linker is essential for stabilizing the closed state of the mHCN2 channel by forming interactions with the opposite subunit. MD simulations revealed that both cAMP and K464E induce a rotation of the intracellular domain relative to the channel pore, weakening the autoinhibitory effect of the unoccupied CL-CNBD region. The adopted poses are in excellent agreement with structural results.
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    Genetic regulation of photoperiod-dependent flowering time in barley (Hordeum vulgare L.)
    (None, 2023-11) Helmsorig, Gesa
    Supplemental Datasets S1 - S8 from the manuscript "FLOWERING LOCUS T1 is a pleiotropic regulator of reproductive development, plant architecture, and source-sink relations in barley", part of the dissertation "Genetic regulation of photoperiod-dependent flowering time in barley (Hordeum vulgare L.)".
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    Loss of Bmal1 impairs the glutamatergic light input to the SCN in mice
    (NA, 2024-12-03) Korkmaz, Hüseyin; Anstötz, Max; Wellinghof, Tim; Fazari, Benedetta; Hallenberger, Angelika; Bergmann, Ann Kathrin; Niggetiedt, Elena; Güven, Delal; Tundo-Lavalle, Federica; Purath, Fathima Faiba A.; Bochinsky, Kevin; Gremer, Lothar; Willbold, Dieter; von Gall, Charlotte; Ali, Amira A. H.
    Introduction: Glutamate represents the dominant neurotransmitter that conveys the light information to the brain, including the suprachiasmatic nucleus (SCN), the central pacemaker for the circadian system. The neuronal and astrocytic glutamate transporters are crucial for maintaining efficient glutamatergic signaling. In the SCN, glutamatergic nerve terminals from the retina terminate on vasoactive intestinal polypeptide (VIP) neurons, which are essential for circadian functions. Up-to-date, little is known about the role of the core circadian clock gene, Bmal1, in glutamatergic neurotransmission of light signal to various brain regions. Methods: The aim of this study was to further elucidate the role of Bmal1 in glutamatergic neurotransmission from the retina to the SCN. We therefore examined the spontaneous rhythmic locomotor activity, neuronal and glial glutamate transporters, as well as the ultrastructure of the synapse between the retinal ganglion cells (RGCs) and the SCN in adult male Bmal1-/- mice. Results: We found that the deletion of Bmal1 affects the light-mediated behavior in mice, decreases the retinal thickness and affects the vesicular glutamate transporters (vGLUT1,2) in the retina. Within the SCN, the immunoreaction of vGLUT1,2, glial glutamate transporters (GLAST) and VIP was decreased while the glutamate concentration was elevated. At the ultrastructure level, the presynaptic terminals were enlarged and the distance between the synaptic vesicles and the synaptic cleft was increased, indicative of a decrease in the readily releasable pool at the excitatory synapses in Bmal1-/-. Conclusion: Our data suggests that Bmal1 deletion affects the glutamate transmission at the tripartite synapse between the ipRGCs and the VIP neurons in the SCN and affects the behavioral responses to light.
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    Manual for FCFit
    (No, 2022) Schmitt, Michael; Krügler, Daniel
    Manual for FCFit