@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} } @misc{Breitbach2018, type = {Master Thesis}, author = {Breitbach, Paula}, title = {Molecular Binding Kinetics of CYP P450 by Using the Infinitesimal Generator Approach}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-69076}, year = {2018}, language = {en} } @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} } @misc{Bender2019, type = {Master Thesis}, author = {Bender, Wilhelm}, title = {On a Novel Approach for Global Optimization of Non-Convex Problems}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-77074}, year = {2019}, abstract = {In this work new approaches for global optimization are developed. We move from theoretical connections in complexity theory to very practical results in protein-ligand docking. In regard to the efficiency of the suggested optimizer, continuity methods are motivated, that yield an improved optimization method.}, language = {en} }