The Biomolecular Interactions Research Group studies protein-protein and protein-drug interactions using biophysical/biochemical techniques. There is a strong interest in systems biology, and the analysis spans a wide spectrum: from atomic resolution structures to cellular behavior. The main focus is on complexes involved in cellular signaling. We use in vitro techniques such as three-dimensional structure determination, protein-protein interaction and enzymatic activity measurements as well as cell based assays. These mechanistic studies are often complemented by large-scale experimental approaches and systems-level computational simulations. The goal of the systems-level studies is the identification of new protein-protein complexes through which the cell’s signaling machinery could be specifically targeted to affect cell growth and death. Our mission is the discovery of new pharmaceutical strategies to combat cancer and chronic inflammation. We design new drugs by screening compound libraries and develop hit compounds through structure based rational design.

Protein kinases in cell signaling

Lots of diseases (e.g. cancer, chronic inflammation) emerge due to some mechanistic malfunctions in signaling networks. Our cells are subjected to diverse extracellular stimuli and they need to respond accordingly to complex patterns of inputs. The sensing of millions of these extracellular inputs, intracellular processing, and triggering the activation of the correct downstream effector proteins are all done by a heavily interconnected protein network. The effector proteins may be metabolic enzymes, transcription factors, or proteins involved in cell movements, which are regulated by protein phosphorylation. The latter is carried out by proteins kinases, and these enzymes also bind to each other and build kinase cascades. The intracellular signaling pathways controlling cell growth and death are “coming together” via complexes of protein kinases.

The portrait of a molecular switch involved in promoting cellular growth. The figure shows the crystal structure of the ERK2-RSK1 protein kinase complex (ERK2 in orange and RSK1 in gray). The yellow segment in the gray molecule works as a molecular switch, if it is modified by the orange molecule then the former gets turned on, and this ultimately will promote growth in cells.

Protein kinases are often targeted by proteins from pathogens and we can learn a great deal on how protein kinase-based cellular networks could be artificially manipulated by studying these proteins. The ORF45 protein from Kaposi’s sarcoma herpesvirus (KSHV) binds to the active ERK-RSK complex and promotes cell growth. After exploring the molecular logic of protein-protein binding within the ternary complex and by carrying out computational simulations based on a mechanistically correct model including other interaction partners, we can understand how the viral protein hijacks this important complex for the up-regulation of a cell growth promoting signaling pathway. ORF45 “attacks” pivotal protein-protein surfaces on ERK and RSK by short linear motifs that are also used to make physical links to the enzyme’s natural protein partners (e.g. upstream kinases, phosphataes, and substrate). It is interesting that the same surfaces (or interaction pockets) are also targeted by proteins from the plague bacterium or from the encephalomyelitis virus.

The tricks of a viral protein targeting the ERK-RSK signaling complex. The crystal structure of the ORF45 protein from Kaposi’s sarcoma (magenta) and RSK2 kinase (teal), and the molecular image of the way how the viral protein “attacks” two cell growth controlling enzymes (RSK2 and ERK2, shown in gray surface representation) by short peptide motifs (salmon and yellow, respectively).

Small molecules affecting protein-protein interactions

Current strategies aim to affect cell signaling by directly inhibiting the activity of protein kinases. The modulation of protein kinase function, however, could also be achieved by targeting specific kinase-based protein-protein complexes. Our goal is the synthesis of new drugs that indirectly affect the activity of selected protein kinases, for example by stabilizing inactive complexes or by interfering with an activating protein-protein interaction.

The 3D structure of a central protein kinase heterodimer involved in inflammation and its inhibition by a complex-specific inhibitor. The p38-MK2 complex can adopt two different quaternary structures: 1) inactive (left), which contains non-phosphorylated p38 (salmon) and it displays a parallel conformation regarding the relative orientation of the two kinase domains, 2) anti-parallel active (right), containing phosphorylated p38 (orange). The N-terminal lobes of the kinase domains are colored in gray, while the surface of the C-terminal lobes are colored differently. An anti-inflammatory drug blocks the natural “transition” between the two states of the p38-MK2 complex because it prefers binding to the inactive complex. This compound prevents the activation of the pro-inflammatory enzyme, MK2 (blue/green), by stabilizing the structure of the inactive p38-MK2 complex.

Publications:

https://vm.mtmt.hu//search/slist.php?nwi=1&inited=1&ty_on=1&url_on=1&cite_type=2&orderby=3D1a&lang=1&location=mtmt&stn=1&AuthorID=10013627

Fontosabb publikációk (2012-2022):

A non-catalytic herpesviral protein reconfigures ERK-RSK signaling by targeting kinase docking systems in the host.

Alexa A, Sok P, Gross F, Albert K, Kobori E, Póti ÁL, Gógl G, Bento I, Kuang E, Taylor SS, Zhu F, Ciliberto A, Reményi A.

Nat Commun. 2022 Jan 25;13(1):472. doi: 10.1038/s41467-022-28109-x

Co-regulation of the transcription controlling ATF2 phosphoswitch by JNK and p38.

Kirsch K, Zeke A, Tőke O, Sok P, Sethi A, Sebő A, Kumar GS, Egri P, Póti ÁL, Gooley P, Peti W, Bento I, Alexa A, Reményi A.

Nat Commun. 2020 Nov 13;11(1):5769. doi: 10.1038/s41467-020-19582-3

MAP Kinase-Mediated Activation of RSK1 and MK2 Substrate Kinases.

Sok P, Gógl G, Kumar GS, Alexa A, Singh N, Kirsch K, Sebő A, Drahos L, Gáspári Z, Peti W,Reményi A.

Structure. 2020 Oct 6;28(10):1101-1113.e5. doi: 10.1016/j.str.2020.06.007

Disordered Protein Kinase Regions in Regulation of Kinase Domain Cores.

Gógl G, Kornev AP, Reményi A*, Taylor SS*

Trends Biochem Sci. 2019 Apr;44(4):300-311. doi: 10.1016/j.tibs.2018.12.002.

Dynamic control of RSK complexes by phosphoswitch-based regulation.

Gógl G, Biri-Kovács B, Póti ÁL, Vadászi H, Szeder B, Bodor A, Schlosser G, Ács A, Turiák L, Buday L, Alexa A, Nyitray L, Reményi A.

FEBS J. 2018 Jan;285(1):46-71. doi: 10.1111/febs.14311

Systematic discovery of linear binding motifs targeting an ancient protein interaction surface on MAP kinases.

Zeke A, Bastys T, Alexa A, Garai Á, Mészáros B, Kirsch K, Dosztányi Z, Kalinina OV, Reményi A.

Mol Syst Biol. 2015 Nov 3;11(11):837. doi: 10.15252/msb.20156269

The Structure of an NDR/LATS Kinase-Mob Complex Reveals a Novel Kinase-Coactivator System and Substrate Docking Mechanism.

Gógl G, Schneider KD, Yeh BJ, Alam N, Nguyen Ba AN, Moses AM, Hetényi C, Reményi A*, Weiss EL*

PLoS Biol. 2015 May 12;13(5):e1002146. doi: 10.1371/journal.pbio.1002146

Structural assembly of the signaling competent ERK2-RSK1 heterodimeric protein kinase complex.

Alexa A, Gógl G, Glatz G, Garai Á, Zeke A, Varga J, Dudás E, Jeszenői N, Bodor A, Hetényi C, Reményi A.

Proc Natl Acad Sci U S A. 2015 Mar 3;112(9):2711-6. doi: 10.1073/pnas.1417571112.

Structural mechanism for the specific assembly and activation of the extracellular signal regulated kinase 5 (ERK5) module.

Glatz G, Gógl G, Alexa A, Reményi A.

J Biol Chem. 2013 Mar 22;288(12):8596-8609. doi: 10.1074/jbc.M113.452235

Specificity of linear motifs that bind to a common mitogen-activated protein kinase docking groove.

Garai Á, Zeke A, Gógl G, Törő I, Fördős F, Blankenburg H, Bárkai T, Varga J, Alexa A, Emig D, Albrecht M, Reményi A.

Sci Signal. 2012 Oct 9;5(245):ra74. doi: 10.1126/scisignal.2003004

International collaborations:

Susan S. Taylor – University of California – San Diego, USA

Andrea Ciliberto – IFOM, Milánó, Olaszország

Eric L. Weiss – Northwestern University, USA

Marie Bogoyevitch – University of Melbourne, Ausztrália

Krishna Rajalingam – Johannes Gutenberg-Universität Mainz, Németország

EU-OPENSCREEN: http://www.eu-openscreen.eu/

Leader

Attila Reményi

Alumni

MSc

Ágnes Szonja Garai (ELTE biology)

Gergő Gógl (ELTE chemistry)

Ferenc Förős (ELTE biology)

Martina Rádli (ELTE biology)

Gábor Glatz (ELTE biology)

Boglárka Zámbó (ELTE biology)

Sarolt Magyary (ELTE chemistry)

Evelin Németh (ELTE chemistry)

Tamás Takács (ELTE biology)

Orsolya Ember (ELTE chemistry)

Bettina Balázs (SE medicine)

PhD

Gábor Glatz

Ágnes Szonja Garai

Gergő Gógl

András Zeke

Klára Kirsch

Sing Neha

Post-doc

Imre Törő

Domonkos Bartis

Krisztina Paál

András Zeke

Eszter Szarka Kállainé

Péter Egri

Members

Current research interests

Synthesis and characterization of pi-extended antiaromatics

A large part of our research efforts is directed towards the synthesis and characterization of unusual pi-systems that contain antiaromatic subunits. Besides the fundamental interest in understanding structure, bonding and reactivity of such polycyclic conjugated systems, pi-extended antiaromatics could be a useful compound class in molecular electronics applications.

Polydopamine-based surface chemistry

Polydopamine is a synthetic polymer inspired by mussel-adhesives that can be simply produced by the oxidative polymerization of dopamine. It is a general adherent, able to stick to essentially any surface. Furthermore, owing to the catechol moieties present in its structure, the polymer exhibits redox activity. Our group is interested in exploiting this polymer in applications ranging from heterogeneous catalysis to photoswitchable interfaces.

Recent publications:

Construction and Properties of Donor–Acceptor Stenhouse Adducts on Gold Surfaces

Dalma Edit Nánási, Attila Kunfi, Ágnes Ábrahám, Péter J. Mayer, Judith Mihály, Gergely F. Samu, Éva Kiss, Miklós Mohai and Gábor London  Langmuir 2021, 37, 10, 3057.

A photoresponsive palladium complex of an azopyridyl-triazole ligand: light-controlled solubility drives catalytic activity in the Suzuki coupling reaction

Attila Kunfi, István Jablonkai, Tamás Gazdag, Péter J. Mayer, Péter Pál Kalapos, Krisztina Németh, Tamás Holczbauer and Gábor London RSC Adv., 2021, 11, 23419.

Photoinduced changes in aromaticity facilitate electrocyclization of dithienylbenzene switches 

Baswanth Oruganti, Péter Pál Kalapos, Varada Bhargav, Gábor London and Bo Durbeej J. Am. Chem. Soc. 2020, 142, 13941.

Structure-property relationships in unsymmetric bis(antiaromatics): Who wins the battle between pentalene and benzocyclobutadiene?

Péter J. Mayer, Ouissam El Bakouri, Tamás Holczbauer, Gergely F. Samu, Csaba Janáky, Henrik Ottosson and Gábor London J. Org. Chem. 2020, 85, 5158.

Photoswitchable Macroscopic Solid Surfaces Based on Azobenzene‐Functionalized Polydopamine/Gold Nanoparticle Composite Materials: Formation, Isomerization and Ligand Exchange

Attila Kunfi, Rita Bernadett Vlocskó, Zsófia Keresztes, Miklós Mohai, Imre Bertóti, Ágnes Ábrahám, Éva Kiss and Gábor London ChemPlusChem 2020, 85, 797.

Leader

Gábor London

Members

A Lendület program további nyerteseiről az MTA.hu honlapján olvashatnak.

Dr. Tóth’s homepage at the University of Cambridge

Leader

Gergely Tóth

Members

Working on the border of chemistry and biology, the main research interests of the group are to

• explore the role of astrocytes in modulating neuronal function in the healthy and diseased brain
• identify potentially druggable (primarily astrocytic) target proteins or mechanisms in pathophysiological conditions
• develop and apply toxicological test platforms for drug development projects

The applied multidisciplinary approaches include in vitro and in vivo simultaneous fluorescent imaging and electrophysiology, toxicology, synthetic chemistry.

Current Research Projects

Contribution of astrocytes to neuronal synchronization in health and disease

Astrocytes have long been considered to have only supporting role in the central nervous system. Substantial advances in the past two decades, however, identified them as important players in the modulation of physiological neuronal function and various pathophysiological conditions and diseases (Héja, 2014). Recently, we investigated whether astrocytic Ca²⁺ transients, an established readout of astroglial activity follows the activation pattern of neurons monitored by electrophysiological or optical methods. We demonstrated (Kékesi et al., 2015) that astrocytes show highly synchronized activity after the onset of recurrent neuronal epileptiform discharges which evolves into astrocytic seizure-like events. Therefore, we showed that astrocytes do have the capability to induce neuronal synchronization in epilepsy.

To extend the above studies we are also exploring whether astrocytes contribute to the emergence of physiological synchronous activity in the neuronal network, like the sleep-associated slow wave activity that plays a major role in memory consolidation. To this end we use Ca²⁺ sensor expressing rat lines developed in cooperation with the Biomembrane Research Group (Institute of Enzimology). These rat lines have been successfully used for simultaneous in vivo monitoring of neuronal and astrocytic activity during sleep. We demonstrate that synchronization of the astrocytic network precedes the build-up of neuronal synchronization, suggesting a causal role of the astrocytic syncytium in the generation of slow wave activity.

Both astrocytes and neurons are active during in vivo slow wave activity. A: In vivo imaging of GCaMP2 expressing stable transgenic rat line. B: Expression of GCaMP2 (green), labeling of astrocytes with intravenously applied SR101 (red). Both neurons (arrows) and astrocytes (arrowheads) express GCaMP2. C: Simultaneous recording of local field potential (LFP) and corresponding Ca2+ transients in a neuron (black) and an astrocyte (red) during slow wave activity.

Astroglial neurotransmitter transporters and gap junctions as potential anti-epileptic drugs

We have previously shown that astrocytes are able to significantly contribute to the tonic inhibition of neurons by releasing GABA. The glial Glu/GABA exchange (Héja et al., 2009, 2012) mechanism has been shown to be triggered by glial uptake of synaptically released Glu. The negative feedback provided by the astrocytes is proportional to the network activity, making this mechanism an attractive target for antiepileptic drug (AED) development that holds considerable promise for finding way to a market niche. Important players in the mechanism, the putrescine-GABA synthetic pathway and the expression of GAT-3 are upregulated under epileptic conditions, further supporting the role of the Glu/GABA exchange in epilepsy. From a pharmacological point of view, it is also important to note that the widely used AEDs levetiracetam and clobazam have been demonstrated to increase GAT-3 expression in the hippocampus.

Schematic representation of the Glu/GABA exchange

In addition to the GABA and Glu transporters, we also showed that blockade of intercellular gap junctional communication between astrocytes decreased the astrocytic synchronization and consequently inhibited or completely prevented the generation of recurrent SLEs. Therefore, the potential glial targets in AED development also includes another glial protein, the gap junction forming connexin43.

Hepatocyte-Kupffer cell cultures as advanced toxicity platforms

Our group is interested in the evaluation of the role of hepatic uptake and efflux transporters in drug induced liver injury, in the pharmacokinetic behavior of drugs and drug candidates and studying drug-transporter interactions. We also investigate drug induced induction and inhibition of phase I, phase II metabolic enzymes and biliary transport proteins. We succeeded in the elaboration of an in vitro hepatic model based on a primary hepatocyte and Kupffer cell co-culture system for studying the role of nonparenchimal cells in drug induced hepatotoxicity. Cytotoxicity assays, Ca²⁺ homeostasis measurements, assays for the expression, localization and function of phase I, phase II metabolic enzymes, uptake and efflux transporters are applied using sandwich culture of hepatocytes originated from different species (human, rodents, and dog).

We develop and characterize a novel hepatocyte–Kupffer cell co-culture based in vitro model for toxicological screening of drugs and nanoparticles. Toxicity investigation are provided regularly to other groups within the center.

To support hepatotoxicity studies we also synthesize fluorescent bile acids due to their role in fat digestion and absorption. By the use of fluorescent bile acids the mechanism of numerous transporters such as OATPs (organic anion transport proteins) and BSEP (bile salt export pump) proteins can be studied. Multistep synthesis of NBD (4-nitrobenzo-2-oxa-1,3-diazole)-labeled bile acids provides valuables conjugates for bioassays.

Equipment and facilities

• FEMTONICS 2D two-photon microscope with simultaneous electrophysiological detection, Ti-Sapphire laser
• OLYMPUS FV300 confocal laser scanning microscope with lasers 458 nm, 488 nm, 514 nm, 543 nm, 633 nm, infrared camera (CCDIR XC-EI50) and simultaneous electrophysiological detection
• Setup for electrophysiology with simultaneous optical detection comprising OLYMPUS BX51WI microscope, Axopatch 200B and Multiclamp 700A amplifiers, Digidata 1320 and Digidata 1322A converters & 5 MHz Micromax CCD camera, NeuroPDA-III, WuTech H-469IV photodiode matrix array
• Laboratories for receptor and transporter pharmacological studies, micro-centrifuges, filtration equipments
• Multi-mode microplate readers for radioactivity or fluorescence detection
• Cell and tissue culture laboratories, cold rooms
• HPLC, fluorimeter, ultracentrifuge, Western blot equipment, deep-freezers
• Access to the Radioisotope laboratory of the Centre, liquid scintillation counters
• Access to the Animal House core facility of the Centre
• Access to the Human Brain Tissue Sample Bank, Semmelweis University, Budapest

Collaborations

• Semmelweis University
• Eötvös University
• Biological Research Centre, HAS
• Szent István University
• Catholic University of Louvain,
• Charité, Berlin
• University of Copenhagen
• Biopredic International, France
• University of Rennes
• Richter Gedeon Pharmaceuticals
• Solvo Biotechnology
• Toxi Coop

Educational Activities

• PhD programs of Eötvös University, Technical University of Budapest and Semmelweis University, Budapest
• Master Program of the University of Technology and Economics, Budapest and Szent István University, Gödöllő

Selected Publications

Kardos J, Szabó Z, Héja L. J Med Chem, 2016, 59:777-787
Kékesi O, Ioja E, Szabó Zs, Kardos J, Héja L. Front Cell Neurosci 2015, 9: 215
Héja L, Nyitrai G, Kékesi O, Dobolyi A, Szabó P, Fiáth R, Ulbert I, Pál-Szenthe B, Palkovits M, Kardos J. BMC Biol. 2012, 10:26
Carta M, Lanore F, Rebola N, Szabo Z, Da Silva SV, Lourenço J, Verraes A, Nadler A, Schultz C, Blanchet C, Mulle C. Neuron 2014, 81:787.
Okiyoneda T, Veit G, Dekkers JF, Bagdany M, Soya N, Xu H, Roldan A, Verkman AS, Kurth M, Simon A, Hegedus T, Beekman JM, Lukacs GL. Nature Chem Biol. 2013, 9:444.
Jemnitz K, Szabo M, Batai-Konczos A, Szabo P, Magda B, Veres Z. Drug Metab Lett. 2015, 9:17-27.
Szabo M, Veres Z, Baranyai Z, Jakab F, Jemnitz K. PLoS One 2013, 8:e59432.

Leader

László Héja

Members

The theoretical and computational studies in our research group are primarily aimed at exploring the mechanism of catalytic processes, and characterizing the structure, physicochemical properties and reactivity of new compounds. Additionally, we examine the properties of redox systems, the behavior of solutions, and recently we are involved in developing molecular databases as well. In mechanistic and reactivity studies, we carry out accurate quantum chemical calculations and molecular dynamics simulations, whereas we use semiempirical quantum chemical methods and machine learning approaches as well in database developments.

University students who are interested in computational chemistry are welcome in our research group.

Asymmetric catalysis

One of the major challenges in synthetic chemistry is to achieve high degree of enantioselectivity, which is generally attained by using chiral catalysts. Computational chemistry can greatly assist the synthetic developments , as computational modelling provides direct information about the structure and energetics of transition states leading to enantiomeric products. This information can be used to interpret the stereoselectivity (or the lack of stereoselectivity) observed experimentally, but computations may even give useful predictions for the design of new reactions. In this project, we examine catalytic reactions of current interest in synthetic chemistry, such as asymmetric catalytic hydrogenation, enantioselective halocyclization, and asymmetric amine catalysis.

Related publications:

• A. Hamza, K. Sorochkina, B. Kótai, K. Chernichenko, D. Berta, M. Bolt, M. Nieger, T. Repo, I. Pápai, Correlating electronic and catalytic properties of frustrated Lewis pairs for imine hydrogenation, ACS Catal. 10, 14290 (2020)
  10.1021/acscatal.0c04263
• A. Hamza, D. Moock, C. Schlepphorst, J. Schneidewind, W. Baumann, F. Glorius, Unveiling a key catalytic pocket for the ruthenium NHC-catalysed asymmetric heteroarene hydrogenation, Chem. Sci. 13, 985 (2022)
  10.1039/D1SC06409F
• D. von der Heiden, F. B. Németh, M. Andreasson, D. Sethio, I. Pápai, M. Erdelyi, Are bis(pyridine)iodine(i) complexes applicable for asymmetric halogenation?, Org. Biomol. Chem. 19, 8307 (2021)
  10.1039/D1OB01532J

Photochemistry and excited state reactivity

One of the most actively studied areas of chemistry today is the use of solar energy to create or break chemical bonds. The key factor is to understand the reaction mechanism. For this purpose, computational chemistry is indispensable as it allows to describe the change in electronic structure upon excitation by light, which is either too expensive or impossible to observe directly via experiments. Computations can also accurately predict photophysical properties such as UV-vis spectra, solvatochromic behaviors, charge transfer characters or excited state redox potentials of molecules not yet synthesized. With this knowledge, we can identify promising photoactive molecules or exclude inactive ones to make synthesis more efficient. Our group is engaged in the study of excited state reaction mechanisms, which includes the area of photocatalysis. We also contribute to the design of novel fluorescent probe molecules. In method development, we design approaches for UV-vis spectrum prediction.

Related publications:

• A. Adamoczky, T. Nagy, P. P. Fehér, V. Pardi-Tóth, Á. Kuki, L. Nagy, M. Zsuga, S. Kéki, Isocyanonaphthol Derivatives: Excited-State Proton Transfer and Solvatochromic Properties, Int. J. Mol. Sci. 23, 7250 (2022)
  10.3390/ijms23137250
• P. P. Fehér, Á. Madarász, A. Stirling, Multiscale Modeling of Electronic Spectra Including Nuclear Quantum Effects, J. Chem. Theory Comput. 17, 6340 (2021)
  10.1021/acs.jctc.1c00531
• P. P. Fehér, Density Functional Theory Evaluation of a Photoinduced Intramolecular Aryl Ether Rearrangement, J. Org. Chem. 86, 2706 (2021)
  10.1021/acs.joc.0c02706

Nuclear quantum effects

The atomic level description of chemical reactions often requires the consideration of nuclear quantum effects. In this project we intend to assess the importance of these effects via theoretical chemical methods. We wish to introduce further developments to our GSTA procedure and assess its applicability. Based on available experimental data and path-integral molecular dynamics simulations, we develop and test new methods that can be applied to characterize various properties of compounds and solvents used in chemical synthesis and catalysis. We primarily focus on thermodynamic properties, but we analyze the structural, kinetic, and spectroscopic properties as well.

Related publications:

• D. Berta, D. Ferenc, I. Bakó, A. Madarász, Nuclear quantum effects from the analysis of smoothed trajectories: Pilot study for water, J. Chem. Theory Comput. 16, 3316 (2020)
  10.1021/acs.jctc.9b00703
• I. Bakó, Á. Madarász, L. Pusztai, Nuclear quantum effects: Their relevance in neutron diffraction studies of liquid water, J. Mol. Liq. 325, 115192 (2021)
  10.1016/j.molliq.2020.115192
• P. Fehér, Á. Madarász, A. Stirling, Multiscale Modeling of Electronic Spectra Including Nuclear Quantum Effects, J. Chem. Theory Comput. 17, 6340 (2021)
  10.1021/acs.jctc.1c00531

Hydration of macromolecules

When it comes to reactions taking place in protic solvents, the reacting molecules form complex H-bonding networks with the environment. To characterize the topology of these H-bonded structures, we apply statistical physics and network theory methods. Using various parameters obtained from quantum chemical calculations, we investigate the strength and the nature of the H-bonds formed between the solute molecule and the surrounding water molecules. This project focuses on hydrated macromolecules (sugars, proteins, DNA, cyclodextrins) and we examine the effect hydration on the native structures and the dynamic properties of these species. We explore the influence of the nuclear quantum effects on structural, dynamic and thermodynamic properties using the GSTA method.

Related publications:

• Sz. Pothoczki, I. Pethes, L. Pusztai, L. Temleitner, K. Ohara, I. Bakó, Properties of Hydrogen-Bonded Networks in Ethanol–Water Liquid Mixtures as a Function of Temperature: Diffraction Experiments and Computer Simulations, J. Phys. Chem. B 125, 6272 (2021)
  10.1021/acs.jpcb.1c03122
• A. Pethes, I. Bakó, L. Pusztai, Chloride ions as integral parts of hydrogen bonded networks in aqueous salt solutions: the appearance of solvent separated anion pairs, Phys. Chem. Chem. Phys. 22, 11038 (2020)
  10.1039/D0CP01806F

Related publications:

The participants of the EU Horizon 2020 CompBat project aimed at identifying new prospective organic molecules for next generation redox flow batteries. In this project, our research group focuses on the development of computational procedures that enable large-scale virtual screening of molecules. We use various cheminformatics tools and quantum chemical methods to construct extended molecular databases, and we apply machine learning approaches to assist the screening. Our database currently includes the structures and standard reduction potentials of over 10.000 organic molecules. The related stability studies and the results of deep learning applications may provide useful guidance for synthetic developments and electrochemical studies.

Further Information:

• The website of the CompBat project
• Short movie introducing our research group (English subtitles are available)

Collaborations

• University of Jyväskylä, Finland
• University of Helsinki, Finland
• University of Bari, Italy
• Universitat Autonoma de Barcelona, Spain
• University of Girona, Spain
• Angstrom Laboratory, Uppsala University, Sweden

Education

• PhD supervision (Hevesy György PhD School of Chemistry, Eötvös Loránd University)
• Bachelor and master thesis supervision (ELTE TTK, BME)

Leader

Imre Pápai

Members

We are part of the COST EpiChemBio Action.

Publications

Total of 47 publications in 2013 – 2016

2016

Söveges, B.; Imre, T.; Szende, T.; Póti, Á. L.; Cserép, G. B.; Hegedűs, T.; Kele, P.; Németh, K., Systematic study of protein labeling by fluorogenic probes using cysteine targeting vinyl sulfone-cyclooctyne tags, Org. Biomol. Chem. 2016, doi: 10.1039/c6ob00810k.

Kozma, E.; Nikić, I.; Varga, B. R.; Aramburu, I. V.; Kang, J. H.; Fackler, O. T.; Lemke E. A.; Kele, P., Hydrophilic trans-Cyclooctenylated Non-Canonical Amino Acids for Fast Intracellular Protein Labeling, ChemBioChem 2016, doi: 10.1002/cbic.201600284.

Knorr, G.; Kozma, E.; Herner, A.; Lemke, E. A.; Kele, P., New, red-emitting tetrazine-phenoxazine fluorogenic labels for live-cell intracellular bioorthogonal labeling schemes, Chem. Eur. J. 2016, doi: 10.1002/chem.201600590.

Demeter, O.; Fodor, E. A.; Kállay, M.; Mező, G.; Németh, K.; Szabó, P. T.; Kele, P., A Double-Clicking Bis-Azide Fluorogenic Dye for Bioorthogonal Self-Labeling Peptide Tags, Chem. Eur. J. 2016, 22, 6382-6388.

Eördögh, Á.; Steinmeyer, J.; Peewasan, K.; Schepers, U.; Wagenknecht, H-A.; Kele, P., Polarity sensitive bioorthogonally applicable far-red emitting labels for postsynthetic nucleic acid labeling by copper-catalyzed and copper-free cycloaddition, Bioconjugate Chem. 2016, 27(2), 457-464.

2015

Cserép, G. B.; Herner, A.; Kele, P., Bioorthogonal fluorescent labels: a review on combined forces, Methods Appl. Fluoresc. 2015, 3(4), 042001.

Domonkos, C.; Zsila, F.; Fitos, I.; Visy, J.; Kassai, R.; Bálint, B.; Kotschy, A., Synthesis and serum protein binding of novel ring-substituted harmine derivatives, RSC Adv. 2015, 5, 53809-53818.

Cserép, G. B.; Demeter, O.; Bätzner, E.; Kállay, M.; Wagenknecht, H-A.; Kele, P., Synthesis and Evaluation of Nicotinic Acid Derived Tetrazines for Bioorthogonal Labeling, Synthesis 2015, 47, 2738-2744.

Castillo, G.; Pribransky, K.; Mező, G.; Kocsis, L.; Csámpai, A.; Németh, K.; Keresztes, Zs.; Hianik, T., Electrochemical and Photometric Detection of Plasmin by Specific Peptide Substrate, Electroanalysis 2015, 27(3), 789-798.

Huber, M. C.; Schreiber, A.; von Olshausen, P.; Varga, B. R.; Kretz, O.; Joch, B.; Barnert, S.; Schubert, R.; Eimer, S.; Kele, P.; Schiller, S. M., Designer amphiphilic proteins as building blocks for the intracellular formation of organelle-like compartments, Nat. Mater. 2015, 14, 125-132.

2014

Domonkos, C.; Fitos, I.; Visy, J.; Zsila, F., Role of the conformational flexibility of evodiamine in its binding to protein hosts: a comparative spectroscopic and molecular modeling evaluation with rutaecarpine, Phys. Chem. Chem. Phys. 2014, 16(41), 22632-22642.

Németh, K.; Domonkos, C.; Sarnyai, V.; Szemán, J.; Jicsinszky, L.; Szente, L.; Visy, J., Cationic permethylated 6-monoamino-6-monodeoxy-β-cyclodextrin as chiral selector of dansylated amino acids in capillary electrophoresis, J. Pharm. Biomed. Anal. 2014, 99, 16-21.

Stubinitzky, C.; Cserép, G. B.; Bätzner, E.; Kele, P.; Wagenknecht, H-A., 2’-Deoxyuridine Conjugated with a Reactive Monobenzocyclooctyne as a DNA Building Block for Copper-Free Click-type Postsynthetic Modification of DNA, Chem. Commun. 2014, 50, 11218-11221.

Herner, A.; Girona, G. E.; Nikić, I.; Kállay, M.; Lemke, E. A.; Kele, P., New Generation of Bioorthogonally Applicable Fluorogenic Dyes with Visible Excitations and Large Stokes Shifts, Bioconjugate Chem. 2014, 25(7), 1370-1374.

Cserép, G. B.; Baranyai, Zs.; Komáromy, D.; Horváti, K.; Bősze, Sz.; Kele, P., Fluorogenic tagging of peptides via Cys residues using thiol-specific vinyl sulfone affinity tags, Tetrahedron 2014, 70, 5961-5965.

Bobály, B.; Tóth, E.; Drahos, L.; Zsila, F.; Visy, J.; Fekete, J.; Vékey, K., Influence of acid-induced conformational variability on protein separation in reversed phase high performance liquid chromatography, J. Chromatogr. A 2014, 1325, 155-162.

2013

Cserép, G. B.; Herner, A.; Wolfbeis, O. S.; Kele, P., Tyrosine specific sequential labeling of proteins, Bioorg. Med. Chem. Lett. 2013, 23, 5776-5778.

Herner, A.; Nikić, I.; Kállay, M.; Lemke, E. A.; Kele, P., A new family of bioorthogonally applicable fluorogenic labels, Org. Biomol. Chem. 2013, 11, 3297-3306.

Cserép, G. B.; Enyedi, K. N.; Demeter, A.; Mező, G.; Kele, P., NIR Mega-Stokes Fluorophores for Bioorthogonal Labeling and Energy Transfer Systems – An Efficient Quencher for Daunomycin, Chem. Asian J. 2013, 8, 494-502.

Kele, P.; Li, X.; Duerkop, A., New luminescent ruthenium probes for detection of diacetyl, Microchem. J. 2013, 108, 156-160.

Educational activity

• Introduction to modern biology (Eötvös University) – fall semester
• Introduction to bioorthogonal chemistry (Eötvös University) – spring semester
• Introduction to molecular recognition (Eötvös University) – spring semester

Collaborations

• Edward Lemke, EMBL, Heidelberg, Germany
• Hans-Achim Wagenknecht, Karlsruhe Institute of Technology, Karlsruhe, Germany
• Stefan Schiller, University of Freiburg, Freiburg, Germany
• Shixin Ye-Lehmann, ENS-Paris, Paris, France

Leader

Péter Kele

Members