@article{GuerlerMollWeberetal.2008, author = {Guerler, A. and Moll, Sebastian and Weber, Marcus and Meyer, Holger and Cordes, Frank}, title = {Selection and flexible optimization of binding modes from conformation ensembles}, volume = {92}, journal = {Biosystems}, number = {1}, doi = {DOI: 10.1016/j.biosystems.2007.11.004}, pages = {42 -- 48}, year = {2008}, language = {en} } @article{HaackRoeblitzScharkoietal.2010, author = {Haack, Fiete and R{\"o}blitz, Susanna and Scharkoi, Olga and Schmidt, Burkhard and Weber, Marcus}, title = {Adaptive Spectral Clustering for Conformation Analysis}, volume = {1281}, journal = {AIP Conference Proceedings}, number = {1}, publisher = {AIP}, doi = {10.1063/1.3498116}, pages = {1585 -- 1588}, year = {2010}, language = {en} } @incollection{DurmazFackeldeyWeber2011, author = {Durmaz, Vedat and Fackeldey, Konstantin and Weber, Marcus}, title = {A rapidly Mixing Monte Carlo Method for the Simulation of Slow Molecular Processes}, booktitle = {Applications of Monte Carlo Methods in Biology, Medicine and Other Fields of Science}, editor = {Mode, Ch.}, publisher = {InTech}, year = {2011}, language = {en} } @article{GuerlerMollWeberetal.2007, author = {G{\"u}rler, A. and Moll, Sebastian and Weber, Marcus and Meyer, Holger and Cordes, Frank}, title = {Selection and flexible optimization of binding modes from conformation ensembles}, journal = {Biosystems}, year = {2007}, language = {en} } @article{KubeWeber2007, author = {Kube, Susanna and Weber, Marcus}, title = {A Coarse Graining Method for the Identification of Transition rates between Molecular Conformations}, volume = {126}, journal = {Journal of Chemical Physics}, number = {2}, doi = {10.1063/1.2404953}, year = {2007}, language = {en} } @inproceedings{WeberKube2005, author = {Weber, Marcus and Kube, Susanna}, title = {Robust Perron Cluster Analysis for Various Applications in Computational Life Science}, booktitle = {Computational Life Sciences}, pages = {57 -- 66}, year = {2005}, language = {en} } @article{MetznerWeberSchuette2010, author = {Metzner, Ph. and Weber, Marcus and Sch{\"u}tte, Christof}, title = {Observation uncertainty in reversible Markov chains}, volume = {82}, journal = {Phys. Rev. E}, number = {3}, publisher = {American Physical Society}, doi = {10.1103/PhysRevE.82.031114}, pages = {031114}, year = {2010}, language = {en} } @article{KlimmBujotzekWeber2011, author = {Klimm, Martina and Bujotzek, Alexander and Weber, Marcus}, title = {Direct Reweighting Strategies in Conformation Dynamics}, volume = {65(2)}, journal = {MATCH Commun. Math. Comp. Chem.}, pages = {333 -- 346}, year = {2011}, language = {en} } @inproceedings{KubeWeber2008, author = {Kube, Susanna and Weber, Marcus}, title = {Computation of equilibrium densities in metastable dynamical systems by domain decomposition}, 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} } @article{ScheibeBujotzekDerneddeetal.2011, author = {Scheibe, Ch. and Bujotzek, Alexander and Dernedde, Jens and Weber, Marcus and Seitz, O.}, title = {DNA-programmed spatial screening of carbohydrate-lectin interactions}, volume = {2}, journal = {Chem. Sci.}, pages = {770 -- 775}, year = {2011}, language = {en} } @article{SiegelAndraeProskeetal.2010, author = {Siegel, D. and Andrae, Karsten and Proske, Matthias and Kochan, C. and Koch, Matthias and Weber, Marcus and Nehls, Irene}, title = {Dynamic covalent hydrazine chemistry as a specific extraction and cleanup technique for the quantification of the Fusarium mycotoxin zearalenone in edible oils}, volume = {1217(15)}, journal = {Journal of Chromatography A}, pages = {2206 -- 15}, year = {2010}, language = {en} } @phdthesis{Weber2006, author = {Weber, Marcus}, title = {Meshless Methods in Conformation Dynamics}, year = {2006}, language = {en} } @incollection{WeberRungsarityotinSchliep2006, author = {Weber, Marcus and Rungsarityotin, Wasinee and Schliep, Alexander}, title = {An Indicator for the Number of Clusters}, booktitle = {From Data and Information Analysis to Knowledge Engineering}, editor = {Spiliopoulou, Myra and Kruse, Rudolf and Borgelt, Christian and N{\"u}rnberger, Andreas and Gaul, Wolfgang}, publisher = {Springer Berlin Heidelberg}, pages = {103 -- 110}, year = {2006}, language = {en} } @article{WeberAndrae2010, author = {Weber, Marcus and Andrae, Karsten}, title = {A simple method for the estimation of entropy differences}, volume = {63(2)}, journal = {MATCH Commun. Math. Comp. Chem. 2010}, pages = {319 -- 332}, year = {2010}, language = {en} } @article{WeberBeckerKoeppenetal.2008, author = {Weber, Marcus and Becker, Roland and K{\"o}ppen, Robert and Durmaz, Vedat}, title = {Classical hybrid Monte-Carlo simulations of the interconversion of hexabromocyclododecane}, volume = {34}, journal = {Journal of Molecular Simulation}, number = {7}, pages = {727 -- 736}, year = {2008}, language = {en} } @article{WeberBujotzekAndraeetal.2011, author = {Weber, Marcus and Bujotzek, Alexander and Andrae, Karsten and Weinhart, M. and Haag, Rainer}, title = {Computational entropy estimation of linear polyether modified surfaces and correlation with protein resistant properties of such surfaces}, journal = {J. Mol. Sim.}, year = {2011}, language = {en} } @article{FoersterBrauerFuersteetal.2007, author = {F{\"o}rster, C. and Brauer, Arnd B. E. and F{\"u}rste, J. and Betzel, C. and Weber, Marcus and Cordes, Frank and Erdmann, V.}, title = {Visualization of the tRNA(Ser) acceptor step binding site in the seryl-tRNA synthetase}, volume = {362}, journal = {BBRC}, number = {2}, pages = {415 -- 418}, year = {2007}, language = {en} } @inproceedings{KubeWeber2008, author = {Kube, Susanna and Weber, Marcus}, title = {Preserving the Markov Property of Reduced Reversible Markov Chains}, 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{WeberKubeWalteretal.2007, author = {Weber, Marcus and Kube, Susanna and Walter, Lionel and Deuflhard, Peter}, title = {Stable Computation of Probability Densities of Metastable Dynamical Systems}, volume = {6}, journal = {SIAM J. Multiscale Model. Simul.}, number = {2}, pages = {396 -- 416}, year = {2007}, language = {en} } @article{KoeppenRiedelProskeetal.2012, author = {K{\"o}ppen, Robert and Riedel, Juliane and Proske, Matthias and Drzymala, Sarah and Rasenko, Tatjana and Durmaz, Vedat and Weber, Marcus and Koch, Matthias}, title = {Photochemical trans-/cis-isomerization and quantification of zearalenone in edible oils}, volume = {60}, journal = {J. Agric. Food Chem.}, doi = {10.1021/jf3037775}, pages = {11733 -- 11740}, year = {2012}, language = {en} } @article{DurmazWeberBecker2012, author = {Durmaz, Vedat and Weber, Marcus and Becker, Roland}, title = {How to Simulate Affinities for Host-Guest Systems Lacking Binding Mode Information: application to the liquid chromatographic separation of hexabromocyclododecane stereoisomers}, volume = {18}, journal = {Journal of Molecular Modeling}, doi = {10.1007/s00894-011-1239-5}, pages = {2399 -- 2408}, year = {2012}, language = {en} } @article{WeberBujotzekHaag2012, author = {Weber, Marcus and Bujotzek, Alexander and Haag, Rainer}, title = {Quantifying the rebinding effect in multivalent chemical ligand-receptor systems}, volume = {137}, journal = {J. Chem. Phys.}, number = {5}, pages = {054111}, year = {2012}, language = {en} } @inproceedings{FackeldeyBujotzekWeber2012, author = {Fackeldey, Konstantin and Bujotzek, Alexander and Weber, Marcus}, title = {A meshless discretization method for Markov state models applied to explicit water peptide folding simulations}, volume = {89}, booktitle = {Meshfree Methods for Partial Differential Equations VI}, publisher = {Springer}, pages = {141 -- 154}, year = {2012}, language = {en} } @article{FastingSchalleyWeberetal.2012, author = {Fasting, Carlo and Schalley, Christoph A. and Weber, Marcus and Seitz, Oliver and Hecht, Stefan and Koksch, Beate and Dernedde, Jens and Graf, Christina and Knapp, Ernst-Walter and Haag, Rainer}, title = {Multivalency as a Chemical Organization and Action Principle}, volume = {51}, journal = {Angew. Chem. Int. Ed.}, number = {42}, pages = {10472 -- 10498}, year = {2012}, 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}, volume = {228}, journal = {Journal of Computational Physics}, number = {6}, doi = {10.1016/j.jcp.2008.11.016}, pages = {1947 -- 1962}, year = {2008}, language = {en} } @misc{KellermannWeberBujotzek2007, author = {Kellermann, R. and Weber, Marcus and Bujotzek, Alexander}, title = {Vom Dietrich zum Sicherheitsschl{\"u}ssel - Mathematiker des Matheon simulieren neuen Wirkstoff f{\"u}r die Diabetes-Behandlung}, number = {2}, publisher = {DFG-Forschungszentrum Matheon}, year = {2007}, language = {en} } @article{KoeppenBeckerWeberetal.2009, author = {K{\"o}ppen, Robert and Becker, Roland and Weber, Marcus and Durmaz, Vedat and Nehls, Irene}, title = {HBCD stereoisimers: Thermal interconversion and enantiospecific trace analysis in biota}, volume = {70}, journal = {Organohalogen Compounds}, pages = {910 -- 913}, year = {2009}, language = {en} } @article{BujotzekWeber2009, author = {Bujotzek, Alexander and Weber, Marcus}, title = {Efficient Simulation of Ligand-Receptor Binding Processes Using the Conformation Dynamics Approach}, volume = {7(5)}, journal = {Journal of Bioinformatics and Computational Biology}, pages = {811 -- 831}, year = {2009}, language = {en} } @incollection{Weber2009, author = {Weber, Marcus}, title = {Spurenstoffe im Trinkwasser - Risikoqualifizierung im Rechner?}, booktitle = {Schriftenreihe des Vereins f{\"u}r Wasser-, Boden- und Lufthygiene}, editor = {Dunemann, L. and Schmoll, O.}, year = {2009}, language = {en} } @article{WeberDurmazBeckeretal.2009, author = {Weber, Marcus and Durmaz, Vedat and Becker, Roland and Esslinger, Susanne}, title = {Predictive Identification of Pentabromocyclododecane (PBCD) Isomers with high Binding Affinity to hTTR}, volume = {71}, journal = {Organohalogen Compounds}, pages = {247 -- 252}, year = {2009}, language = {en} } @article{FackeldeyKlimmWeber2012, author = {Fackeldey, Konstantin and Klimm, Martina and Weber, Marcus}, title = {A Coarse Graining Method for the Dimension Reduction of the State Space of Biomolecules}, volume = {5}, journal = {Journal of Mathematical Chemistry}, number = {9}, pages = {2623 -- 2635}, year = {2012}, language = {en} } @article{RoeblitzWeber2009, author = {R{\"o}blitz, Susanna and Weber, Marcus}, title = {Fuzzy Spectral Clustering by PCCA+}, journal = {Classification and Clustering: Models, Software and Applications}, number = {WIAS Report No. 26}, pages = {73 -- 79}, year = {2009}, language = {en} } @article{RoeblitzWeber2013, author = {R{\"o}blitz, Susanna and Weber, Marcus}, title = {Fuzzy spectral clustering by PCCA+: application to Markov state models and data classification}, volume = {7}, journal = {Advances in Data Analysis and Classification}, number = {2}, doi = {10.1007/s11634-013-0134-6}, pages = {147 -- 179}, year = {2013}, language = {en} } @article{ScharkoiEsslingerBeckeretal.2014, author = {Scharkoi, Olga and Esslinger, Susanne and Becker, Roland and Weber, Marcus and Nehls, Irene}, title = {Predicting sites of cytochrome P450-mediated hydroxylation applied to CYP3A4 and hexabromocyclododecane}, journal = {Molecular Simulation}, doi = {10.1080/08927022.2014.898845}, year = {2014}, language = {en} } @article{HaackFackeldeyRoeblitzetal.2013, 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}, volume = {139}, journal = {The Journal of Chemical Physics}, doi = {10.1063/1.4830409}, pages = {110 -- 194}, year = {2013}, language = {en} } @inproceedings{IgdeWoelkRoeblitzetal.2015, author = {Igde, Sinaida and W{\"o}lk, Hendrik and R{\"o}blitz, Susanna and Reidelbach, Marco and Weber, Marcus and Hartmann, Laura}, title = {Identifying Multivalent Binding Kinetics of Precision Glycomacromolecules: A Kinetic Study Using kinITC}, booktitle = {M{\"u}nster Symposium on Cooperative Effects 2015 - SFB 858, at Westf{\"a}lische Wilhelms-Universit{\"a}t M{\"u}nster, 2015}, year = {2015}, abstract = {Multivalent sugar/protein interactions are well-known to proceed through different binding modes 1-5 which in turn can be described by their binding kinetics 3-5. This study provides additional insight into the association and dissociation reaction rates of complex multivalent sugar/protein interactions. Binding kinetics of recently introduced multivalent precision glycomacromolecules 6-8 to Concanavalin A (Con A) were studied by " kinetic Isothermal Titration Calorimetry " (kinITC) 9-11. The effect of multivalency is evaluated by comparing rate constants of glycomacromolecules obtaining the same and different valency of mannose ligands and by variation of the overall backbone properties, such as hydrophilic/ hydrophoboc. In addition, binding kinetics were studied using different conformations of Con A (homodimer vs.-tetramer) and thus a different protein valency. Our results show that precision glycomacromolecule/Con A binding proceeds non-cooperatively. Further, association and dissociation rates are mainly described by intermolecular complex formation. Together with the so-called functional valency, we can discriminate between " bound " and " unbound " states for macroscopic on-and off-rates, even for such complex glycooligomer/protein systems. By comparing e.g. a mono-to a divalent glycomacromolecule for their binding to dimeric Con A, we see a lower dissociation rate for the latter. As both bind monovalently to Con A, this is a strong indication for a statistical rebinding event. Further, there is a strong dependence of multivalent binding kinetics on the ligand density of glycomacromolecules as well as the Con A conformation and thus the overall on-and off-rates.}, language = {en} } @article{QuerDonatiKelleretal.2018, author = {Quer, Jannes and Donati, Luca and Keller, Bettina and Weber, Marcus}, title = {An automatic adaptive importance sampling algorithm for molecular dynamics in reaction coordinates}, volume = {40}, journal = {SIAM Journal on Scientific Computing}, number = {2}, doi = {10.1137/17m1124772}, pages = {A653 -- A670}, year = {2018}, abstract = {In this article we propose an adaptive importance sampling scheme for dynamical quantities of high dimensional complex systems which are metastable. The main idea of this article is to combine a method coming from Molecular Dynamics Simulation, Metadynamics, with a theorem from stochastic analysis, Girsanov's theorem. The proposed algorithm has two advantages compared to a standard estimator of dynamic quantities: firstly, it is possible to produce estimators with a lower variance and, secondly, we can speed up the sampling. One of the main problems for building importance sampling schemes for metastable systems is to find the metastable region in order to manipulate the potential accordingly. Our method circumvents this problem by using an assimilated version of the Metadynamics algorithm and thus creates a non-equilibrium dynamics which is used to sample the equilibrium quantities.}, language = {en} } @article{Weber2018, author = {Weber, Marcus}, title = {Transformationsprodukte im Kl{\"a}rwerk: Mathematische Ans{\"a}tze der Bewertung}, journal = {KA Korrespondenz Abwasser, Abfall}, year = {2018}, language = {de} } @article{ReuterWeberFackeldeyetal.2018, author = {Reuter, Bernhard and Weber, Marcus and Fackeldey, Konstantin and R{\"o}blitz, Susanna and Garcia, Martin E.}, title = {Generalized Markov State Modeling Method for Nonequilibrium Biomolecular Dynamics: Exemplified on Amyloid β Conformational Dynamics Driven by an Oscillating Electric Field}, volume = {14}, journal = {Journal of Chemical Theory and Computation}, number = {7}, doi = {10.1021/acs.jctc.8b00079}, pages = {3579 -- 3594}, year = {2018}, abstract = {Markov state models (MSMs) have received an unabated increase in popularity in recent years, as they are very well suited for the identification and analysis of metastable states and related kinetics. However, the state-of-the-art Markov state modeling methods and tools enforce the fulfillment of a detailed balance condition, restricting their applicability to equilibrium MSMs. To date, they are unsuitable to deal with general dominant data structures including cyclic processes, which are essentially associated with nonequilibrium systems. To overcome this limitation, we developed a generalization of the common robust Perron Cluster Cluster Analysis (PCCA+) method, termed generalized PCCA (G-PCCA). This method handles equilibrium and nonequilibrium simulation data, utilizing Schur vectors instead of eigenvectors. G-PCCA is not limited to the detection of metastable states but enables the identification of dominant structures in a general sense, unraveling cyclic processes. This is exemplified by application of G-PCCA on nonequilibrium molecular dynamics data of the Amyloid β (1-40) peptide, periodically driven by an oscillating electric field.}, language = {en} } @article{WagnerZapataWanetal.2018, author = {Wagner, Sabine and Zapata, Carlos and Wan, Wei and Gawlitza, Kornelia and Weber, Marcus and Rurack, Knut}, title = {Role of Counterions in Molecularly Imprinted Polymers for Anionic Species}, volume = {34}, journal = {Langmuir}, number = {23}, doi = {10.1021/acs.langmuir.8b00500}, pages = {6963 -- 6975}, year = {2018}, abstract = {Small-molecule oxoanions are often imprinted noncovalently as carboxylates into molecularly imprinted polymers (MIPs), requiring the use of an organic counterion. Popular species are either pentamethylpiperidine (PMP) as a protonatable cation or tetraalkylammonium (TXA) ions as permanent cations. The present work explores the influence of the TXA as a function of their alkyl chain length, from methyl to octyl, using UV/vis absorption, fluorescence titrations, and HPLC as well as MD simulations. Protected phenylalanines (Z-L/D-Phe) served as templates/analytes. While the influence of the counterion on the complex stability constants and anion-induced spectral changes shows a monotonous trend with increasing alkyl chain length at the prepolymerization stage, the cross-imprinting/rebinding studies showed a unique pattern that suggested the presence of adaptive cavities in the MIP matrix, related to the concept of induced fit of enzyme-substrate interaction. Larger cavities formed in the presence of larger counterions can take up pairs of Z-x-Phe and smaller TXA, eventually escaping spectroscopic detection. Correlation of the experimental data with the MD simulations revealed that counterion mobility, the relative distances between the three partners, and the hydrogen bond lifetimes are more decisive for the response features observed than actual distances between interacting atoms in a complex or the orientation of binding moieties. TBA has been found to yield the highest imprinting factor, also showing a unique dual behavior regarding the interaction with template and fluorescent monomer. Finally, interesting differences between both enantiomers have been observed in both theory and experiment, suggesting true control of enantioselectivity. The contribution concludes with suggestions for translating the findings into actual MIP development.}, language = {en} } @article{SpahnDelVecchioRodriguezGaztelumendietal.2018, author = {Spahn, Viola and Del Vecchio, Giovanna and Rodriguez-Gaztelumendi, Antonio and Temp, Julia and Labuz, Dominika and Kloner, Michael and Reidelbach, Marco and Machelska, Halina and Weber, Marcus and Stein, Christoph}, title = {Opioid receptor signaling, analgesic and side effects induced by a computationally designed pH-dependent agonist}, volume = {8}, journal = {Scientific Reports}, publisher = {Springer Nature}, pages = {8965}, year = {2018}, abstract = {Novel pain killers without adverse effects are urgently needed.}, language = {en} } @article{ErlekamIgdeRoeblitzetal.2019, author = {Erlekam, Franziska and Igde, Sinaida and R{\"o}blitz, Susanna and Hartmann, Laura and Weber, Marcus}, title = {Modeling of Multivalent Ligand-Receptor Binding Measured by kinITC}, volume = {7}, journal = {Computation}, number = {3}, doi = {10.3390/computation7030046}, pages = {46}, year = {2019}, abstract = {In addition to the conventional Isothermal Titration Calorimetry (ITC), kinetic ITC (kinITC) not only gains thermodynamic information, but also kinetic data from a biochemical binding process. Moreover, kinITC gives insights into reactions consisting of two separate kinetic steps, such as protein folding or sequential binding processes. The ITC method alone cannot deliver kinetic parameters, especially not for multivalent bindings. This paper describes how to solve the problem using kinITC and an invariant subspace projection. The algorithm is tested for multivalent systems with different valencies.}, language = {en} } @article{Weber2019, author = {Weber, Marcus}, title = {Transformationsprodukte im Kl{\"a}rwerk: Mathematische Ans{\"a}tze der Bewertung}, volume = {7}, journal = {KA Korrespondenz Abwasser, Abfall}, pages = {551 -- 557}, year = {2019}, language = {de} } @article{VenkatareddyWilkeErnstetal.2019, author = {Venkatareddy, Narendra Lagumaddepalli and Wilke, Patrick and Ernst, Natalia and Horch, Justus and Weber, Marcus and Dallmann, Andre and B{\"o}rner, Hans G.}, title = {Mussel-glue inspired adhesives: A study on the relevance of L-Dopa and the function of the sequence at nanomaterial-peptide interfaces}, volume = {6}, journal = {Advanced Materials Interfaces}, number = {13}, doi = {10.1002/admi.201900501}, pages = {1900501}, year = {2019}, abstract = {Mussel glue-proteins undergo structural transitions at material interfaces to optimize adhesive surface contacts. Those intriguing structure responses are mimicked by a mussel-glue mimetic peptide (HSY*SGWSPY*RSG (Y* = l-Dopa)) that was previously selected by phage-display to adhere to Al2O3 after enzymatic activation. Molecular level insights into the full-length adhesion domain at Al2O3 surfaces are provided by a divergent-convergent analysis, combining nuclear Overhauser enhancement based 2D NOESY and saturation transfer difference NMR analysis of submotifs along with molecular dynamics simulations of the full-length peptide. The peptide is divided into two submotifs, each containing one Dopa "anchor" (Motif-1 and 2). The analysis proves Motif-1 to constitute a dynamic Al2O3 binder and adopting an "M"-structure with multiple surface contacts. Motif-2 binds stronger by two surface contacts, forming a compact "C"-structure. Taking these datasets as constraints enables to predict the structure and propose a binding process model of the full-length peptide adhering to Al2O3.}, language = {en} } @article{DelVecchioLabuzTempetal.2019, author = {Del Vecchio, Giovanna and Labuz, Dominika and Temp, Julia and Seitz, Viola and Kloner, Michael and Negrete, Roger and Rodriguez-Gaztelumendi, Antonio and Weber, Marcus and Machelska, Halina and Stein, Christoph}, title = {pKa of opioid ligands as a discriminating factor for side effects}, volume = {9}, journal = {Scientific Reports}, doi = {10.1038/s41598-019-55886-1}, pages = {19344}, year = {2019}, abstract = {The non-selective activation of central and peripheral opioid receptors is a major shortcoming of currently available opioids. Targeting peripheral opioid receptors is a promising strategy to preclude side effects. Recently, we showed that fentanyl-derived μ-opioid receptor (MOR) agonists with reduced acid dissociation constants (pKa) due to introducing single fluorine atoms produced injury-restricted antinociception in rat models of inflammatory, postoperative and neuropathic pain. Here, we report that a new double-fluorinated compound (FF6) and fentanyl show similar pKa, MOR affinity and [35S]-GTPγS binding at low and physiological pH values. In vivo, FF6 produced antinociception in injured and non-injured tissue, and induced sedation and constipation. The comparison of several fentanyl derivatives revealed a correlation between pKa values and pH-dependent MOR activation, antinociception and side effects. An opioid ligand's pKa value may be used as discriminating factor to design safer analgesics.}, language = {en} } @article{VillatoroZuehlkeRiebeetal.2020, author = {Villatoro, Jos{\´e} and Z{\"u}hlke, Martin and Riebe, Daniel and Beitz, Toralf and Weber, Marcus and L{\"o}hmannsr{\"o}ben, Hans-Gerd}, title = {Sub-ambient pressure IR-MALDI ion mobility spectrometer for the determination of low and high field mobilities}, volume = {412}, journal = {Analytical and Bioanalytical Chemistry}, doi = {10.1007/s00216-020-02735-0}, pages = {5247 -- 5260}, year = {2020}, abstract = {A new ion mobility (IM) spectrometer, enabling mobility measurements in the pressure range between 5 and 500 mbar and in the reduced field strength range E/N of 5-90 Td, was developed and characterized. Reduced mobility (K0) values were studied under low E/N (constant value) as well as high E/N (deviation from low field K0) for a series of molecular ions in nitrogen. Infrared matrix-assisted laser desorption ionization (IR-MALDI) was used in two configurations: a source working at atmospheric pressure (AP) and, for the first time, an IR-MALDI source working with a liquid (aqueous) matrix at sub-ambient/reduced pressure (RP). The influence of RP on IR-MALDI was examined and new insights into the dispersion process were gained. This enabled the optimization of the IM spectrometer for best analytical performance. While ion desolvation is less efficient at RP, the transport of ions is more efficient, leading to intensity enhancement and an increased number of oligomer ions. When deciding between AP and RP IR-MALDI, a trade-off between intensity and resolving power has to be considered. Here, the low field mobility of peptide ions was first measured and compared with reference values from ESI-IM spectrometry (at AP) as well as collision cross sections obtained from molecular dynamics simulations. The second application was the determination of the reduced mobility of various substituted ammonium ions as a function of E/N in nitrogen. The mobility is constant up to a threshold at high E/N. Beyond this threshold, mobility increases were observed. This behavior can be explained by the loss of hydrated water molecules.}, language = {en} } @article{WeberWeitereAutoren2020, author = {Weber, Marcus and Weitere Autoren,}, title = {DIN SPEC 2343: {\"U}bertragung von sprachbasierten Daten zwischen K{\"u}nstlichen Intelligenzen - Festlegung von Parametern und Formaten}, journal = {Beuth Verlag}, editor = {Reichardt, Christine}, year = {2020}, abstract = {Dieses Dokument legt Parameter und Formate f{\"u}r die {\"U}bertragung sprachbasierter Daten zwischen verschiedenen KI-{\"O}kosystemen fest.}, language = {de} } @article{RabbenRayWeber2020, author = {Rabben, Robert Julian and Ray, Sourav and Weber, Marcus}, title = {ISOKANN: Invariant subspaces of Koopman operators learned by a neural network}, volume = {153}, journal = {The Journal of Chemical Physics}, number = {11}, doi = {10.1063/5.0015132}, pages = {114109}, year = {2020}, abstract = {The problem of determining the rate of rare events in dynamical systems is quite well-known but still difficult to solve. Recent attempts to overcome this problem exploit the fact that dynamic systems can be represented by a linear operator, such as the Koopman operator. Mathematically, the rare event problem comes down to the difficulty in finding invariant subspaces of these Koopman operators K. In this article, we describe a method to learn basis functions of invariant subspaces using an artificial neural Network.}, language = {en} } @misc{RaySunkaraSchuetteetal.2020, author = {Ray, Sourav and Sunkara, Vikram and Sch{\"u}tte, Christof and Weber, Marcus}, title = {How to calculate pH-dependent binding rates for receptor-ligand systems based on thermodynamic simulations with different binding motifs}, issn = {1438-0064}, doi = {10.1080/08927022.2020.1839660}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-78437}, year = {2020}, abstract = {Molecular simulations of ligand-receptor interactions are a computational challenge, especially when their association- (``on''-rate) and dissociation- (``off''-rate) mechanisms are working on vastly differing timescales. In addition, the timescale of the simulations themselves is, in practice, orders of magnitudes smaller than that of the mechanisms; which further adds to the complexity of observing these mechanisms, and of drawing meaningful and significant biological insights from the simulation. One way of tackling this multiscale problem is to compute the free-energy landscapes, where molecular dynamics (MD) trajectories are used to only produce certain statistical ensembles. The approach allows for deriving the transition rates between energy states as a function of the height of the activation-energy barriers. In this article, we derive the association rates of the opioids fentanyl and N-(3-fluoro-1-phenethylpiperidin-4-yl)- N-phenyl propionamide (NFEPP) in a \$\mu\$-opioid receptor by combining the free-energy landscape approach with the square-root-approximation method (SQRA), which is a particularly robust version of Markov modelling. The novelty of this work is that we derive the association rates as a function of the pH level using only an ensemble of MD simulations. We also verify our MD-derived insights by reproducing the in vitro study performed by the Stein Lab, who investigated the influence of pH on the inhibitory constant of fentanyl and NFEPP (Spahn et al. 2017). MD simulations are far more accessible and cost-effective than in vitro and in vivo studies. Especially in the context of the current opioid crisis, MD simulations can aid in unravelling molecular functionality and assist in clinical decision-making; the approaches presented in this paper are a pertinent step forward in this direction.}, language = {en} } @article{FackeldeyRoehmNiknejadetal.2021, author = {Fackeldey, Konstantin and R{\"o}hm, Jonas and Niknejad, Amir and Chewle, Surahit and Weber, Marcus}, title = {Analyzing Raman Spectral Data without Separabiliy Assumption}, volume = {3}, journal = {Journal of Mathematical Chemistry}, number = {59}, publisher = {Springer}, arxiv = {http://arxiv.org/abs/2007.06428}, doi = {10.1007/s10910-020-01201-7}, pages = {575 -- 596}, year = {2021}, abstract = {Raman spectroscopy is a well established tool for the analysis of vibration spectra, which then allow for the determination of individual substances in a chemical sample, or for their phase transitions. In the Time-Resolved-Raman-Sprectroscopy the vibration spectra of a chemical sample are recorded sequentially over a time interval, such that conclusions for intermediate products (transients) can be drawn within a chemical process. The observed data-matrix M from a Raman spectroscopy can be regarded as a matrix product of two unknown matrices W and H, where the first is representing the contribution of the spectra and the latter represents the chemical spectra. One approach for obtaining W and H is the non-negative matrix factorization. We propose a novel approach, which does not need the commonly used separability assumption. The performance of this approach is shown on a real world chemical example.}, language = {en} }