This project aims at the creation of a MATH+ success story around the mathematics of drug design. It proposes a new drug design strategy for G-protein coupled receptors by distinguishing between the effects of drugs in healthy and pathological environment. It extends previous projects by (I) coupling the molecular timescales of receptor activation with the associated cellular processes and the adverse side effects induced by them, and by (II) generalizing the new strategy beyond opioid receptors and pain relief towards the treatment of e.g. blood pressure, heart failure, or respiratory failure (e.g. Covid-19).

Figure: The tripeptide Ala-Asp-Ala exists in two forms, protonated and deprotonated, whose occurrence depends on the acidity of the environment. Using SqRA, it is possible to determine the transition rate of the peptide as a function of pH.

Publications

2024
A community effort in SARS-CoV-2 drug discovery Molecular Informatics, 43(1), p. e202300262, 2024 Johannes Schimunek, Philipp Seidl, Katarina Elez, Tim Hempel, Tuan Le, Frank Noé, Simon Olsson, Lluís Raich, Robin Winter, Hatice Gokcan, Filipp Gusev, Evgeny M. Gutkin, Olexandr Isayev, Maria G. Kurnikova, Chamali H. Narangoda, Roman Zubatyuk, Ivan P. Bosko, Konstantin V. Furs, Anna D. Karpenko, Yury V. Kornoushenko, Mikita Shuldau, Artsemi Yushkevich, Mohammed B. Benabderrahmane, Patrick Bousquet-Melou, Ronan Bureau, Beatrice Charton, Bertrand C. Cirou, Gérard Gil, William J. Allen, Suman Sirimulla, Stanley Watowich, Nick Antonopoulos, Nikolaos Epitropakis, Agamemnon Krasoulis, Vassilis Itsikalis, Stavros Theodorakis, Igor Kozlovskii, Anton Maliutin, Alexander Medvedev, Petr Popov, Mark Zaretckii, Hamid Eghbal-Zadeh, Christina Halmich, Sepp Hochreiter, Andreas Mayr, Peter Ruch, Michael Widrich, Francois Berenger, Ashutosh Kumar, Yoshihiro Yamanishi, Kam Y. J. Zhang, Emmanuel Bengio, Yoshua Bengio, Moksh J. Jain, Maksym Korablyov, Cheng-Hao Liu, Gilles Marcou, Enrico Glaab, Kelly Barnsley, Suhasini M. Iyengar, Mary Jo Ondrechen, V. Joachim Haupt, Florian Kaiser, Michael Schroeder, Luisa Pugliese, Simone Albani, Christina Athanasiou, Andrea Beccari, Paolo Carloni, Giulia D’Arrigo, Eleonora Gianquinto, Jonas Goßen, Anton Hanke, Benjamin P. Joseph, Daria B. Kokh, Sandra Kovachka, Candida Manelfi, Goutam Mukherjee, Abraham Muñiz-Chicharro, Francesco Musiani, Ariane Nunes-Alves, Giulia Paiardi, Giulia Rossetti, S. Kashif Sadiq, Francesca Spyrakis, Carmine Talarico, Alexandros Tsengenes, Rebecca C. Wade, Conner Copeland, Jeremiah Gaiser, Daniel R. Olson, Amitava Roy, Vishwesh Venkatraman, Travis J. Wheeler, Haribabu Arthanari, Klara Blaschitz, Marco Cespugli, Vedat Durmaz, Konstantin Fackeldey, Patrick D. Fischer, Christoph Gorgulla, Christian Gruber, Karl Gruber, Michael Hetmann, Jamie E. Kinney, Krishna M. Padmanabha Das, Shreya Pandita, Amit Singh, Georg Steinkellner, Guilhem Tesseyre, Gerhard Wagner, Zi-Fu Wang, Ryan J. Yust, Dmitry S. Druzhilovskiy, Dmitry A. Filimonov, Pavel V. Pogodin, Vladimir Poroikov, Anastassia V. Rudik, Leonid A. Stolbov, Alexander V. Veselovsky, Maria De Rosa, Giada De Simone, Maria R. Gulotta, Jessica Lombino, Nedra Mekni, Ugo Perricone, Arturo Casini, Amanda Embree, D. Benjamin Gordon, David Lei, Katelin Pratt, Christopher A. Voigt, Kuang-Yu Chen, Yves Jacob, Tim Krischuns, Pierre Lafaye, Agnès Zettor, M. Luis Rodríguez, Kris M. White, Daren Fearon, Frank Von Delft, Martin A. Walsh, Dragos Horvath, Charles L. Brooks III, Babak Falsafi, Bryan Ford, Adolfo García-Sastre, Sang Yup Lee, Nadia Naffakh, Alexandre Varnek, Günter Klambauer, Thomas M. Hermans BibTeX
DOI
Math-Powered Drug Design
Augmented ant colony algorithm for virtual drug discovery Journal of Mathematical Chemistry, Vol.62, pp. 367-385, 2024 Luca Donati, Konstantin Fackeldey, Marcus Weber BibTeX
DOI
Math-Powered Drug Design
Multi-grid reaction-diffusion master equation: applications to morphogen gradient modelling 2024 (under review) Radek Erban, Stefanie Winkelmann BibTeX
arXiv
Math-Powered Drug Design
Partial mean-field model for neurotransmission dynamics Mathematical Biosciences, Vol.369, 2024 Alberto Montefusco, Luzie Helfmann, Toluwani Okunola, Stefanie Winkelmann, Christof Schütte BibTeX
arXiv
DOI
Math-Powered Drug Design
Tensor-SqRA: Modeling the transition rates of interacting molecular systems in terms of potential energies Journal of Chemical Physics, Vol.160, p. 104112, 2024 Alexander Sikorski, Amir Niknejad, Marcus Weber, Luca Donati BibTeX
arXiv
DOI
Math-Powered Drug Design
The Kramers turnover in terms of a macro-state projection on phase space Molecular Physics, p. e2356748, 2024 (epub ahead of print) Luca Donati, Christof Schütte, Marcus Weber BibTeX
DOI
Math-Powered Drug Design
2023
A route to the hydrodynamic limit of a reaction-diffusion master equation using gradient structures SIAM Journal on Applied Mathematics, 83(2), pp. 837-861, 2023 Alberto Montefusco, Christof Schütte, Stefanie Winkelmann BibTeX
arXiv
DOI
Math-Powered Drug Design
Accuracy of reaction coordinate based rate theories for modelling chemical reactions: insights from the thermal isomerization in retinal Submitted to The Journal of Physical Chemistry A, 2023 (under review) Simon Ghysbrecht, Luca Donati, Bettina G. Keller BibTeX
arXiv
Math-Powered Drug Design
Coarse Grained MD Simulations of Opioid interactions with the µ-opioid receptor and the surrounding lipid membrane Biophysica, 3(2), pp. 263-275, 2023 Sourav Ray, Konstantin Fackeldey, Christoph Stein, Marcus Weber BibTeX
DOI
Math-Powered Drug Design
Efficient Estimation of Transition Rates as Functions of pH Proceedings in Applied Mathematics & Mechanics, Vol.23, 2023 (epub ahead of print) Luca Donati, Marcus Weber BibTeX
arXiv
DOI
Math-Powered Drug Design
Handlungsempfehlung zur integrativen Bewertung der weitergehenden Abwasserbehandlung von kommunalen Kläranlagen Christian Wilhelm (Ed.), DWA / GDCh, 2023, ISBN: 978-3-96862-563-8 Thomas Ternes, Karl-Heinz Bauer, Frank Brauer, Jörg Drewes, Adriano Joss, Georg Hiller, Kevin Jewell, Jörg Oehlmann, Michael Radke, Ulrike Schulte-Oehlmann, Thomas Schwartz, Peter Seel, Jeanette Völker, Lilo Weber, Marcus Weber BibTeX
Math-Powered Drug Design
Modelling altered signalling of G-protein coupled receptors in inflamed environment to advance drug design Scientific Reports, 13(607), 2023 Arne Thies, Vikram Sunkara, Sourav Ray, Hanna Wulkow, M. Özgür Celik, Fatih Yergöz, Christof Schütte, Christoph Stein, Marcus Weber, Stefanie Winkelmann BibTeX
DOI
Math-Powered Drug Design
Novel multi-objective affinity approach allows to identify pH-specific μ-opioid receptor agonists Journal of Cheminformatics, Vol.15, 2023 Christopher Secker, Konstantin Fackeldey, Marcus Weber, Sourav Ray, Christoph Gorgulla, Christof Schütte BibTeX
DOI
Math-Powered Drug Design
Novel multi-objective affinity approach allows to identify pH-specific μ-opioid receptor agonists (Dataset) 2023 Christopher Secker BibTeX
DOI
URN
Math-Powered Drug Design
Overcoming the Timescale Barrier in Molecular Dynamics: Transfer Operators, Variational Principles, and Machine Learning Acta Numerica, Vol.32, pp. 517-673, 2023 (preprint available as ZIB-Report 22-25) Christof Schütte, Stefan Klus, Carsten Hartmann PDF (ZIB-Report)
BibTeX
DOI
Math-Powered Drug Design
VirtualFlow 2.0 - The Next Generation Drug Discovery Platform Enabling Adaptive Screens of 69 Billion Molecules bioRxiv, 2023 (preprint available as ) Christoph Gorgulla, AkshatKumar Nigam, Matt Koop, Süleyman Selim Çınaroğlu, Christopher Secker, Mohammad Haddadnia, Abhishek Kumar, Yehor Malets, Alexander Hasson, Minkai Li, Ming Tang, Roni Levin-Konigsberg, Dmitry Radchenko, Aditya Kumar, Minko Gehev, Pierre-Yves Aquilanti, Henry Gabb, Amr Alhossary, Gerhard Wagner, Alán Aspuru-Guzik, Yurii S. Moroz, Konstantin Fackeldey, Haribabu Arthanari BibTeX
DOI
Math-Powered Drug Design
2022
A review of Girsanov Reweighting and of Square Root Approximation for building molecular Markov State Models Journal of Mathematical Physics, 63(12), pp. 123306-1-123306-21, 2022 Luca Donati, Marcus Weber, Bettina G. Keller BibTeX
DOI
Math-Powered Drug Design
Assessing transition rates as functions of environmental variables The Journal of Chemical Physics, 157(22), pp. 224103-1-224103-14, 2022 Luca Donati, Marcus Weber BibTeX
DOI
Math-Powered Drug Design
Emerging frontiers in virtual drug discovery: From quantum mechanical methods to deep learning approaches Current Opinion in Chemical Biology, Vol.69, pp. 102156-102156-12, 2022 Christoph Gorgulla, Abhilash Jayaraj, Konstantin Fackeldey, Haribabu Arthanari BibTeX
DOI
Math-Powered Drug Design
SepFree NMF: A Toolbox for Analyzing the Kinetics of Sequential Spectroscopic Data Algorithms, 15(9), p. 297, 2022 Renata Sechi, Konstantin Fackeldey, Surahit Chewle, Marcus Weber BibTeX
DOI
Math-Powered Drug Design
The Impact of Membrane Protein Diffusion on GPCR Signaling Cells, 11(10), p. 1660, 2022 Horst-Holger Boltz, Alexei Sirbu, Nina Stelzer, Primal de Lanerolle, Stefanie Winkelmann, Paolo Annibale BibTeX
DOI
Math-Powered Drug Design