@article{ThiesSunkaraRayetal., author = {Thies, Arne and Sunkara, Vikram and Ray, Sourav and Wulkow, Hanna and Celik, M. {\"O}zg{\"u}r and Yerg{\"o}z, Fatih and Sch{\"u}tte, Christof and Stein, Christoph and Weber, Marcus and Winkelmann, Stefanie}, title = {Modelling altered signalling of G-protein coupled receptors in inflamed environment to advance drug design}, series = {Scientific Reports}, volume = {13}, journal = {Scientific Reports}, number = {607}, doi = {10.1038/s41598-023-27699-w}, abstract = {We previously reported the successful design, synthesis and testing of the prototype opioid painkiller NFEPP that does not elicit adverse side effects. The design process of NFEPP was based on mathematical modelling of extracellular interactions between G-protein coupled receptors (GPCRs) and ligands, recognizing that GPCRs function differently under pathological versus healthy conditions. We now present an additional and novel stochastic model of GPCR function that includes intracellular dissociation of G-protein subunits and modulation of plasma membrane calcium channels and their dependence on parameters of inflamed and healthy tissue (pH, radicals). The model is validated against in vitro experimental data for the ligands NFEPP and fentanyl at different pH values and radical concentrations. We observe markedly reduced binding affinity and calcium channel inhibition for NFEPP at normal pH compared to lower pH, in contrast to the effect of fentanyl. For increasing radical concentrations, we find enhanced constitutive G-protein activation but reduced ligand binding affinity. Assessing the different effects, the results suggest that, compared to radicals, low pH is a more important determinant of overall GPCR function in an inflamed environment. Future drug design efforts should take this into account.}, language = {en} } @article{IgdeRoeblitzMuelleretal., author = {Igde, Sinaida and R{\"o}blitz, Susanna and M{\"u}ller, Anne and Kolbe, Katharina and Boden, Sophia and Fessele, Claudia and Lindhorst, Thisbe and Weber, Marcus and Hartmann, Laura}, title = {Linear Precision Glycomacromolecules with Varying Interligand Spacing and Linker Functionalities Binding to Concanavalin A and the Bacterial Lectin FimH}, series = {Marcomolecular Bioscience}, volume = {17}, journal = {Marcomolecular Bioscience}, number = {12}, doi = {10.1002/mabi.201700198}, pages = {1700198}, language = {en} } @article{HaackFackeldeyRoeblitzetal., author = {Haack, Fiete and Fackeldey, Konstantin and R{\"o}blitz, Susanna and Scharkoi, Olga and Weber, Marcus and Schmidt, Burkhard}, title = {Adaptive spectral clustering with application to tripeptide conformation analysis}, series = {The Journal of Chemical Physics}, volume = {139}, journal = {The Journal of Chemical Physics}, doi = {10.1063/1.4830409}, pages = {110 -- 194}, language = {en} } @article{RoeblitzWeber, author = {R{\"o}blitz, Susanna and Weber, Marcus}, title = {Fuzzy Spectral Clustering by PCCA+}, series = {Classification and Clustering: Models, Software and Applications}, journal = {Classification and Clustering: Models, Software and Applications}, number = {WIAS Report No. 26}, pages = {73 -- 79}, language = {en} } @article{RoeblitzWeber, author = {R{\"o}blitz, Susanna and Weber, Marcus}, title = {Fuzzy spectral clustering by PCCA+: application to Markov state models and data classification}, series = {Advances in Data Analysis and Classification}, volume = {7}, journal = {Advances in Data Analysis and Classification}, number = {2}, doi = {10.1007/s11634-013-0134-6}, pages = {147 -- 179}, language = {en} } @article{KubeLasserWeber2008, author = {Kube, Susanna and Lasser, Caroline and Weber, Marcus}, title = {Monte Carlo sampling of Wigner functions and surface hopping quantum dynamics}, series = {Journal of Computational Physics}, volume = {228}, journal = {Journal of Computational Physics}, number = {6}, doi = {10.1016/j.jcp.2008.11.016}, pages = {1947 -- 1962}, year = {2008}, language = {en} } @article{WeberKubeWalteretal.2007, author = {Weber, Marcus and Kube, Susanna and Walter, Lionel and Deuflhard, Peter}, title = {Stable Computation of Probability Densities of Metastable Dynamical Systems}, series = {SIAM J. Multiscale Model. Simul.}, volume = {6}, journal = {SIAM J. Multiscale Model. Simul.}, number = {2}, pages = {396 -- 416}, year = {2007}, language = {en} } @inproceedings{KubeWeber2008, author = {Kube, Susanna and Weber, Marcus}, title = {Preserving the Markov Property of Reduced Reversible Markov Chains}, series = {Numerical Analysis and Applied Mathematics, International Conference on Numerical Analysis and Applied Mathematics 2008}, volume = {1048}, booktitle = {Numerical Analysis and Applied Mathematics, International Conference on Numerical Analysis and Applied Mathematics 2008}, pages = {593 -- 596}, year = {2008}, language = {en} } @article{KubeWeber2007, author = {Kube, Susanna and Weber, Marcus}, title = {A Coarse Graining Method for the Identification of Transition rates between Molecular Conformations}, series = {Journal of Chemical Physics}, volume = {126}, journal = {Journal of Chemical Physics}, number = {2}, doi = {10.1063/1.2404953}, year = {2007}, language = {en} } @inproceedings{KubeWeber2008, author = {Kube, Susanna and Weber, Marcus}, title = {Computation of equilibrium densities in metastable dynamical systems by domain decomposition}, series = {Numerical Analysis and Applied Mathematics, International Conference on Numerical Analysis and Applied Mathematics 2008}, volume = {1048}, booktitle = {Numerical Analysis and Applied Mathematics, International Conference on Numerical Analysis and Applied Mathematics 2008}, publisher = {AIP Conference Proceedings}, pages = {339 -- 342}, year = {2008}, language = {en} }