@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} } @article{RoehlWeberFackeldey2021, author = {R{\"o}hl, Susanne and Weber, Marcus and Fackeldey, Konstantin}, title = {Computing the minimal rebinding effect for non-reversible processes}, volume = {19}, journal = {Multiscale Modeling and Simulation}, number = {1}, arxiv = {http://arxiv.org/abs/2007.08403}, doi = {https://doi.org/10.1137/20M1334966}, pages = {460 -- 477}, year = {2021}, abstract = {The aim of this paper is to investigate the rebinding effect, a phenomenon describing a "short-time memory" which can occur when projecting a Markov process onto a smaller state space. For guaranteeing a correct mapping by the Markov State Model, we assume a fuzzy clustering in terms of membership functions, assigning degrees of membership to each state. The macro states are represented by the membership functions and may be overlapping. The magnitude of this overlap is a measure for the strength of the rebinding effect, caused by the projection and stabilizing the system. A minimal bound for the rebinding effect included in a given system is computed as the solution of an optimization problem. Based on membership functions chosen as a linear combination of Schur vectors, this generalized approach includes reversible as well as non-reversible processes.}, language = {en} } @article{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}, volume = {46}, journal = {Molecular Simulation}, number = {18}, publisher = {Taylor and Francis}, doi = {10.1080/08927022.2020.1839660}, pages = {1443 -- 1452}, 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. 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 μ-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.}, language = {en} } @article{WeberFischerDamerauetal.2020, author = {Weber, Marie-Christin and Fischer, Lisa and Damerau, Alexandra and Ponomarev, Igor and Pfeiffenberger, Moritz and Gaber, Timo and G{\"o}tschel, Sebastian and Lang, Jens and R{\"o}blitz, Susanna and Buttgereit, Frank and Ehrig, Rainald and Lang, Annemarie}, title = {Macroscale mesenchymal condensation to study cytokine-driven cellular and matrix-related changes during cartilage degradation}, volume = {12}, journal = {Biofabrication}, number = {4}, doi = {10.1088/1758-5090/aba08f}, year = {2020}, abstract = {Understanding the pathophysiological processes of cartilage degradation requires adequate model systems to develop therapeutic strategies towards osteoarthritis (OA). Although different in vitro or in vivo models have been described, further comprehensive approaches are needed to study specific disease aspects. This study aimed to combine in vitro and in silico modeling based on a tissue-engineering approach using mesenchymal condensation to mimic cytokine-induced cellular and matrix-related changes during cartilage degradation. Thus, scaffold-free cartilage-like constructs (SFCCs) were produced based on self-organization of mesenchymal stromal cells (mesenchymal condensation) and i) characterized regarding their cellular and matrix composition or secondly ii) treated with interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) for 3 weeks to simulate OA-related matrix degradation. In addition, an existing mathematical model based on partial differential equations was optimized and transferred to the underlying settings to simulate distribution of IL-1β, type II collagen degradation and cell number reduction. By combining in vitro and in silico methods, we aim to develop a valid, efficient alternative approach to examine and predict disease progression and effects of new therapeutics.}, language = {en} } @misc{WeberDurmazSabrietal.2017, author = {Weber, Marcus and Durmaz, Vedat and Sabri, Peggy and Reidelbach, Marco}, title = {Supplementary simulation data for Science Manuscript ai8636}, doi = {10.12752/5.MWB.1.0}, year = {2017}, abstract = {The simulation data has been produced by Vedat Durmaz, Peggy Sabri and Marco Reidelbach inside the "Computational Molecular Design" Group headed by Marcus Weber at Zuse-Institut Berlin, Takustr. 7, D-14195 Berlin, Germany. The file contains classical simulation data for different fentanyl derivates in the MOR binding pocket at different pHs. It also includes instruction files for quantum-chemical pKa-value estimations and a description of how we derived the pKa-values from the Gaussian09 log-files.}, language = {en} } @misc{Weber2018, author = {Weber, Marcus}, title = {Supplementary: Implications of PCCA+ in Molecular Simulation}, year = {2018}, abstract = {Matlab-software and data sets to recapitulate the presented results in M. Weber: Implications of PCCA+ in Molecular Simulation. Computation, 6(1):20, 2018.}, language = {en} } @article{DjurdjevacConradFuerstenauGrabundzijaetal.2018, author = {Djurdjevac Conrad, Natasa and Fuerstenau, Daniel and Grabundzija, Ana and Helfmann, Luzie and Park, Martin and Schier, Wolfram and Sch{\"u}tt, Brigitta and Sch{\"u}tte, Christof and Weber, Marcus and Wulkow, Niklas and Zonker, Johannes}, title = {Mathematical modeling of the spreading of innovations in the ancient world}, volume = {7}, journal = {eTopoi. Journal for Ancient Studies}, issn = {ISSN 2192-2608}, doi = {10.17171/4-7-1}, year = {2018}, language = {en} } @article{Weber2018, author = {Weber, Marcus}, title = {Implications of PCCA+ in Molecular Simulation}, volume = {6}, journal = {Computation}, number = {1}, doi = {10.3390/computation6010020}, pages = {20}, year = {2018}, abstract = {Upon ligand binding or during chemical reactions the state of a molecular system changes in time. Usually we consider a finite set of (macro-) states of the system (e.g., 'bound' vs. 'unbound'), although the process itself takes place in a continuous space. In this context, the formula chi=XA connects the micro-dynamics of the molecular system to its macro-dynamics. Chi can be understood as a clustering of micro-states of a molecular system into a few macro-states. X is a basis of an invariant subspace of a transfer operator describing the micro-dynamics of the system. The formula claims that there is an unknown linear relation A between these two objects. With the aid of this formula we can understand rebinding effects, the electron flux in pericyclic reactions, and systematic changes of binding rates in kinetic ITC experiments. We can also analyze sequential spectroscopy experiments and rare event systems more easily. This article provides an explanation of the formula and an overview of some of its consequences.}, language = {en} } @article{SchradeTroegerEldashanetal.2018, author = {Schrade, Katharina and Tr{\"o}ger, Jessica and Eldashan, Adeep and Z{\"u}hlke, Kerstin and Abdul Azees, Kamal R. and Elkins, Jonathan M. and Neuenschwander, Martin and Oder, Andreas and Elkewedi, Mohamed and Jaksch, Sarah and Andrae, Karsten and Li, Jinliang and Fernandes, Jaoa and M{\"u}ller, Paul Markus and Grunwald, Stephan and Marino, Stephen F. and Vukicevic, Tanja and Eichhorst, Jenny and Wiesner, Burkhard and Weber, Marcus and Kapiloff, Michael and Rocks, Oliver and Daumke, Oliver and Wieland, Thomas and Knapp, Stefan and von Kries, Jens Peter and Klussmann, Enno}, title = {An AKAP-Lbc-RhoA interaction inhibitor promotes the translocation of aquaporin-2 to the plasma membrane of renal collecting duct principal cells}, volume = {13}, journal = {PLOS ONE}, number = {1}, doi = {10.1371/journal.pone.0191423}, pages = {e0191423 -- e0191423}, year = {2018}, abstract = {Stimulation of renal collecting duct principal cells with antidiuretic hormone (arginine-vasopressin, AVP) results in inhibition of the small GTPase RhoA and the enrichment of the water channel aquaporin-2 (AQP2) in the plasma membrane. The membrane insertion facilitates water reabsorption from primary urine and fine-tuning of body water homeostasis. Rho guanine nucleotide exchange factors (GEFs) interact with RhoA, catalyze the exchange of GDP for GTP and thereby activate the GTPase. However, GEFs involved in the control of AQP2 in renal principal cells are unknown. The A-kinase anchoring protein, AKAP-Lbc, possesses GEF activity, specifically activates RhoA, and is expressed in primary renal inner medullary collecting duct principal (IMCD) cells. Through screening of 18,431 small molecules and synthesis of a focused library around one of the hits, we identified an inhibitor of the interaction of AKAP-Lbc and RhoA. This molecule, Scaff10-8, bound to RhoA, inhibited the AKAP-Lbc-mediated RhoA activation but did not interfere with RhoA activation through other GEFs or activities of other members of the Rho family of small GTPases, Rac1 and Cdc42. Scaff10-8 promoted the redistribution of AQP2 from intracellular vesicles to the periphery of IMCD cells. Thus, our data demonstrate an involvement of AKAP-Lbc-mediated RhoA activation in the control of AQP2 trafficking.}, language = {en} } @article{WeberFischerDamerauetal.2019, author = {Weber, Marie-Christin and Fischer, Lisa and Damerau, Alexandra and Ponomarev, Igor and Pfeiffenberger, Moritz and Gaber, Timo and G{\"o}tschel, Sebastian and Lang, Jens and R{\"o}blitz, Susanna and Buttgereit, Frank and Ehrig, Rainald and Lang, Annemarie}, title = {In vitro and in silico modeling of cellular and matrix-related changes during the early phase of osteoarthritis}, journal = {BioRxiv}, doi = {10.1101/725317}, year = {2019}, abstract = {Understanding the pathophysiological processes of osteoarthritis (OA) require adequate model systems. Although different in vitro or in vivo models have been described, further comprehensive approaches are needed to study specific parts of the disease. This study aimed to combine in vitro and in silico modeling to describe cellular and matrix-related changes during the early phase of OA. We developed an in vitro OA model based on scaffold-free cartilage-like constructs (SFCCs), which was mathematically modeled using a partial differential equation (PDE) system to resemble the processes during the onset of OA. SFCCs were produced from mesenchymal stromal cells and analyzed weekly by histology and qPCR to characterize the cellular and matrix-related composition. To simulate the early phase of OA, SFCCs were treated with interleukin-1β (IL-1β), tumor necrosis factor α (TNFα) and examined after 3 weeks or cultivated another 3 weeks without inflammatory cytokines to validate the regeneration potential. Mathematical modeling was performed in parallel to the in vitro experiments. SFCCs expressed cartilage-specific markers, and after stimulation an increased expression of inflammatory markers, matrix degrading enzymes, a loss of collagen II (Col-2) and a reduced cell density was observed which could be partially reversed by retraction of stimulation. Based on the PDEs, the distribution processes within the SFCCs, including those of IL-1β, Col-2 degradation and cell number reduction was simulated. By combining in vitro and in silico methods, we aimed to develop a valid, efficient alternative approach to examine and predict disease progression and new therapeutic strategies.}, language = {en} } @article{LangFischerWeberetal.2019, author = {Lang, Annemarie and Fischer, Lisa and Weber, Marie-Christin and Gaber, Timo and Ehrig, Rainald and R{\"o}blitz, Susanna and Buttgereit, Frank}, title = {Combining in vitro simulation and in silico modelling towards a sophisticated human osteoarthritis model}, volume = {27}, journal = {Osteoarthritis and Cartilage}, doi = {10.1016/j.joca.2019.02.277}, pages = {S183}, year = {2019}, abstract = {Our project aimed at building an in silico model based on our recently developed in vitro osteoarthritis (OA) model seeking for refinement of the model to enhance validity and translatability towards the more sophisticated simulation of OA. In detail, the previously 3D in vitro model is based on 3D chondrogenic constructs generated solely from human bone marrow derived mesenchymal stromal cells (hMSCs). Besides studying the normal state of the model over 3 weeks, the in vitro model was treated with interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNFα) to mimic an OA-like environment.}, language = {en} } @article{ChewleEmmerlingWeber2020, author = {Chewle, Surahit and Emmerling, Franziska and Weber, Marcus}, title = {Effect of choice of solvent on crystallization pathway of Paracetamol: An experimental and theoretical case study}, volume = {10}, journal = {Crystals}, number = {12}, doi = {10.3390/cryst10121107}, pages = {1107}, year = {2020}, abstract = {The choice of solvents influences crystalline solid formed during the crystallization of active pharmaceutical ingredients (API). The underlying effects are not always well understood because of the complexity of the systems. Theoretical models are often insufficient to describe this phenomenon. In this study, the crystallization behavior of the model drug paracetamol in different solvents was studied based on experimental and molecular dynamics data. The crystallization process was followed in situ using time-resolved Raman spectroscopy. Molecular dynamics with simulated annealing algorithm was used for an atomistic understanding of the underlying processes. The experimental and theoretical data indicate that paracetamol molecules adopt a particular geometry in a given solvent predefining the crystallization of certain polymorphs.}, language = {en} } @article{HartmannJoesterSchuetteetal.2026, author = {Hartmann, Carsten and J{\"o}ster, Annika and Sch{\"u}tte, Christof and Sikorski, Alexander and Weber, Marcus}, title = {Importance sampling of unbounded random stopping times: computing committor functions and exit rates without reweighting}, arxiv = {http://arxiv.org/abs/2601.01489}, year = {2026}, abstract = {Rare events in molecular dynamics are often related to noise-induced transitions between different macroscopic states (e.g., in protein folding). A common feature of these rare transitions is that they happen on timescales that are on average exponentially long compared to the characteristic timescale of the system, with waiting time distributions that have (sub)exponential tails and infinite support. As a result, sampling such rare events can lead to trajectories that can be become arbitrarily long, with not too low probability, which makes the reweighting of such trajectories a real challenge. Here, we discuss rare event simulation by importance sampling from a variational perspective, with a focus on applications in molecular dynamics, in particular the computation of committor functions. The idea is to design importance sampling schemes that (a) reduce the variance of a rare event estimator while controlling the average length of the trajectories and (b) that do not require the reweighting of possibly very long trajectories. In doing so, we study different stochastic control formulations for committor and mean first exit times, which we compare both from a theoretical and a computational point of view, including numerical studies of some benchmark examples.}, language = {en} } @misc{WeberSagerGleixner2018, author = {Weber, Tobias and Sager, Sebastian and Gleixner, Ambros}, title = {Solving Quadratic Programs to High Precision using Scaled Iterative Refinement}, issn = {1438-0064}, doi = {10.1007/s12532-019-00154-6}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-68152}, year = {2018}, abstract = {Quadratic optimization problems (QPs) are ubiquitous, and solution algorithms have matured to a reliable technology. However, the precision of solutions is usually limited due to the underlying floating-point operations. This may cause inconveniences when solutions are used for rigorous reasoning. We contribute on three levels to overcome this issue. First, we present a novel refinement algorithm to solve QPs to arbitrary precision. It iteratively solves refined QPs, assuming a floating-point QP solver oracle. We prove linear convergence of residuals and primal errors. Second, we provide an efficient implementation, based on SoPlex and qpOASES that is publicly available in source code. Third, we give precise reference solutions for the Maros and M{\´e}sz{\´a}ros benchmark library.}, language = {en} } @article{WeberSagerGleixner2019, author = {Weber, Tobias and Sager, Sebastian and Gleixner, Ambros}, title = {Solving Quadratic Programs to High Precision using Scaled Iterative Refinement}, volume = {11}, journal = {Mathematical Programming Computation}, publisher = {Springer Berlin Heidelberg}, doi = {10.1007/s12532-019-00154-6}, pages = {421 -- 455}, year = {2019}, abstract = {Quadratic optimization problems (QPs) are ubiquitous, and solution algorithms have matured to a reliable technology. However, the precision of solutions is usually limited due to the underlying floating-point operations. This may cause inconveniences when solutions are used for rigorous reasoning. We contribute on three levels to overcome this issue. First, we present a novel refinement algorithm to solve QPs to arbitrary precision. It iteratively solves refined QPs, assuming a floating-point QP solver oracle. We prove linear convergence of residuals and primal errors. Second, we provide an efficient implementation, based on SoPlex and qpOASES that is publicly available in source code. Third, we give precise reference solutions for the Maros and M{\´e}sz{\´a}ros benchmark library.}, language = {en} } @misc{CordesWeberSchmidtEhrenberg2002, author = {Cordes, Frank and Weber, Marcus and Schmidt-Ehrenberg, Johannes}, title = {Metastable Conformations via successive Perron-Cluster Cluster Analysis of dihedrals}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-7074}, number = {02-40}, year = {2002}, abstract = {Decomposition of the high dimensional conformational space of bio-molecules into metastable subsets is used for data reduction of long molecular trajectories in order to facilitate chemical analysis and to improve convergence of simulations within these subsets. The metastability is identified by the Perron-cluster cluster analysis of a Markov process that generates the thermodynamic distribution. A necessary prerequisite of this analysis is the discretization of the conformational space. A combinatorial approach via discretization of each degree of freedom will end in the so called ''curse of dimension''. In the following paper we analyze Hybrid Monte Carlo simulations of small, drug-like biomolecules and focus on the dihedral degrees of freedom as indicators of conformational changes. To avoid the ''curse of dimension'', the projection of the underlying Markov operator on each dihedral is analyzed according to its metastability. In each decomposition step of a recursive procedure, those significant dihedrals, which indicate high metastability, are used for further decomposition. The procedure is introduced as part of a hierarchical protocol of simulations at different temperatures. The convergence of simulations within metastable subsets is used as an ''a posteriori'' criterion for a successful identification of metastability. All results are presented with the visualization program AmiraMol.}, language = {en} } @misc{Weber2003, author = {Weber, Marcus}, title = {Improved Perron Cluster Analysis}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-7260}, number = {03-04}, year = {2003}, abstract = {The problem of clustering data can often be transformed into the problem of finding a hidden block diagonal structure in a stochastic matrix. Deuflhard et al. have proposed an algorithm that state s the number \$k\$ of clusters and uses the sign structure of \$k\$ eigenvectors of the stochastic matrix to solve the cluster problem. Recently Weber and Galliat discovered that this system of eigenvectors can easily be transformed into a system of \$k\$ membership functions or soft characteristic functions describing the clusters. In this article we explain the corresponding cluster algorithm and point out the underlying theory. By means of numerical examples we explain how the grade of membership can be interpreted.}, language = {en} } @misc{DeuflhardWeber2003, author = {Deuflhard, Peter and Weber, Marcus}, title = {Robust Perron Cluster Analysis in Conformation Dynamics}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-7415}, number = {03-19}, year = {2003}, abstract = {The key to molecular conformation dynamics is the direct identification of metastable conformations, which are almost invariant sets of molecular dynamical systems. Once some reversible Markov operator has been discretized, a generalized symmetric stochastic matrix arises. This matrix can be treated by Perron cluster analysis, a rather recent method involving a Perron cluster eigenproblem. The paper presents an improved Perron cluster analysis algorithm, which is more robust than earlier suggestions. Numerical examples are included.}, language = {en} } @misc{WeberMeyer2005, author = {Weber, Marcus and Meyer, Holger}, title = {ZIBgridfree - Adaptive Conformation Analysis with qualified Support of Transition States and Thermodynamic Weights}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-8514}, number = {05-17}, year = {2005}, abstract = {This paper introduces a new algorithm of conformational analysis based on mesh-free methods as described in [M. Weber. Mehless methods in Conformation Dynamics.(2005)]. The adaptive decomposition of the conformational space by softly limiting functions avoids trapping effects and allows adaptive refinement strategies. These properties of the algorithm makes ZIBgridfree particularly suitable for the complete exploration of high-dimensional conformational space. The adaptive control of the algorithm benefits from the tight integration of molecular simulation and conformational analysis. An emphasized part of the analysis is the Robust Perron Cluster Analysis (PCCA+) based on the work of Peter Deuflhard and Marcus Weber. PCCA+ supports an almost-characteristic cluster definition with an outstanding mapping of transition states. The outcome is expressed by the metastable sets of conformations, their thermodynamic weights and flexibility.}, language = {en} } @article{AbendrothBujotzekShanetal.2011, author = {Abendroth, Frank and Bujotzek, Alexander and Shan, Min and Haag, Rainer and Weber, Marcus and Seitz, Oliver}, title = {DNA-controlled bivalent presentation of ligands for the estrogen receptor}, journal = {Angew. Chem. Int. Ed.}, year = {2011}, language = {en} } @article{BujotzekShanHaagetal.2011, author = {Bujotzek, Alexander and Shan, Min and Haag, Rainer and Weber, Marcus}, title = {Towards a rational spacer design for bivalent inhibition of estrogen receptor}, volume = {25(3)}, journal = {J. Comput.-Aided Mol. Des.}, pages = {253 -- 262}, year = {2011}, language = {en} } @incollection{DeuflhardWeber2005, author = {Deuflhard, Peter and Weber, Marcus}, title = {Robust Perron Cluster Analysis in Conformation Dynamics}, volume = {398}, booktitle = {Lin. Alg. Appl. - Special Issue on Matrices and Mathematical Biology}, publisher = {Elsevier Journals}, address = {Germany}, pages = {161 -- 184}, year = {2005}, language = {en} } @article{RigortGuentherHegerletal.2012, author = {Rigort, Alexander and G{\"u}nther, David and Hegerl, Reiner and Baum, Daniel and Weber, Britta and Prohaska, Steffen and Medalia, Ohad and Baumeister, Wolfgang and Hege, Hans-Christian}, title = {Automated segmentation of electron tomograms for a quantitative description of actin filament networks}, volume = {177}, journal = {Journal of Structural Biology}, doi = {10.1016/j.jsb.2011.08.012}, pages = {135 -- 144}, year = {2012}, language = {en} } @article{WeberGreenanProhaskaetal.2012, author = {Weber, Britta and Greenan, Garrett and Prohaska, Steffen and Baum, Daniel and Hege, Hans-Christian and M{\"u}ller-Reichert, Thomas and Hyman, Anthony and Verbavatz, Jean-Marc}, title = {Automated tracing of microtubules in electron tomograms of plastic embedded samples of Caenorhabditis elegans embryos}, volume = {178}, journal = {Journal of Structural Biology}, number = {2}, doi = {10.1016/j.jsb.2011.12.004}, pages = {129 -- 138}, year = {2012}, language = {en} } @article{TorsneyWeirSaadMoelleretal.2011, author = {Torsney-Weir, Thomas and Saad, Ahmed and M{\"o}ller, Torsten and Hege, Hans-Christian and Weber, Britta and Verbavatz, Jean-Marc}, title = {Tuner: Principled Parameter Finding for Image Segmentation Algorithms Using Visual Response Surface Exploration}, volume = {17}, journal = {IEEE Trans. Vis. Comput. Graph.}, number = {12}, pages = {1892 -- 1901}, year = {2011}, language = {en} } @article{PoethkowWeberHege2011, author = {P{\"o}thkow, Kai and Weber, Britta and Hege, Hans-Christian}, title = {Probabilistic Marching Cubes}, volume = {30}, journal = {Computer Graphics Forum}, number = {3}, doi = {10.1111/j.1467-8659.2011.01942.x}, pages = {931 -- 940}, year = {2011}, language = {en} } @inproceedings{WeberMoellerVerbavatzetal.2011, author = {Weber, Britta and M{\"o}ller, Marit and Verbavatz, Jean-Marc and Baum, Daniel and Hege, Hans-Christian and Prohaska, Steffen}, title = {Fast Tracing of Microtubule Centerlines in Electron Tomograms}, booktitle = {BioVis 2011 Abstracts, 1st IEEE Symposium on Biological Data Visualization}, year = {2011}, language = {en} } @article{GoubergritsWeberPetzetal.2009, author = {Goubergrits, Leonid and Weber, Sarah and Petz, Christoph and Spuler, Andreas and P{\"o}thke, Jens and Berthe, Andr{\´e} and Hege, Hans-Christian}, title = {Wall-PIV as a Near Wall Flow Validation Tool for CFD}, volume = {12}, journal = {Journal of Visualization}, number = {3}, pages = {241 -- 250}, year = {2009}, language = {en} } @inproceedings{DercksenWeberGuentheretal.2009, author = {Dercksen, Vincent J. and Weber, Britta and G{\"u}nther, David and Oberlaender, Marcel and Prohaska, Steffen and Hege, Hans-Christian}, title = {Automatic alignment of stacks of filament data}, booktitle = {Proc. IEEE International Symposium on Biomedical Imaging}, publisher = {IEEE press}, address = {Boston, USA}, pages = {971 -- 974}, year = {2009}, language = {en} } @article{SahnerWeberLameckeretal.2008, author = {Sahner, Jan and Weber, Britta and Lamecker, Hans and Prohaska, Steffen}, title = {Extraction of feature Lines on surface meshes based on discrete Morse theory}, volume = {27}, journal = {Computer Graphics Forum}, number = {3}, address = {Eindhoven, Netherlands}, doi = {10.1111/j.1467-8659.2008.01202.x}, pages = {735 -- 742}, year = {2008}, language = {en} } @article{KoschekDurmazKrylovaetal.2015, author = {Koschek, and Durmaz, Vedat and Krylova, and Wieczorek, and Gupta, Pooja and Richter, and Bujotzek, Alexander and Fischer, and Haag, Rainer and Freund, and Weber, Marcus and Rademann,}, title = {Peptide polymer ligands for a tandem WW-domain, a soft multivalent protein-protein interaction: lessons on the thermodynamic fitness of flexible ligands}, volume = {11}, journal = {Beilstein J. Org. Chem.}, pages = {837 -- 847}, year = {2015}, language = {en} } @article{DurmazWeberMeyeretal.2015, author = {Durmaz, Vedat and Weber, Marcus and Meyer, and M{\"u}ckter,}, title = {Computergest{\"u}tzte Simulationen zur Absch{\"a}tzung gesundheitlicher Risiken durch anthropogene Spurenstoffe der Wassermatrix}, volume = {3/15}, journal = {KA Korrespondenz Abwasser, Abfall}, pages = {264 -- 267}, year = {2015}, language = {de} } @misc{WeberFackeldey2015, author = {Weber, Marcus and Fackeldey, Konstantin}, title = {G-PCCA: Spectral Clustering for Non-reversible Markov Chains}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-55505}, year = {2015}, abstract = {Spectral clustering methods are based on solving eigenvalue problems for the identification of clusters, e.g., the identification of metastable subsets of a Markov chain. Usually, real-valued eigenvectors are mandatory for this type of algorithms. The Perron Cluster Analysis (PCCA+) is a well-known spectral clustering method of Markov chains. It is applicable for reversible Markov chains, because reversibility implies a real-valued spectrum. We extend this spectral clustering method also to non-reversible Markov chains and give some illustrative examples. The main idea is to replace the eigenvalue problem by a real-valued Schur decomposition. By this extension, non-reversible Markov chains can be analyzed. Furthermore, the chains need not have a positive stationary distribution. And additionally to metastabilities, dominant cycles and sinks can be identified, too.}, language = {en} } @misc{DjurdjevacConradWeberSchuette2015, author = {Djurdjevac Conrad, Natasa and Weber, Marcus and Sch{\"u}tte, Christof}, title = {Finding dominant structures of nonreversible Markov processes}, issn = {1438-0064}, doi = {10.1137/15M1032272}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-55739}, year = {2015}, abstract = {Finding metastable sets as dominant structures of Markov processes has been shown to be especially useful in modeling interesting slow dynamics of various real world complex processes. Furthermore, coarse graining of such processes based on their dominant structures leads to better understanding and dimension reduction of observed systems. However, in many cases, e.g. for nonreversible Markov processes, dominant structures are often not formed by metastable sets but by important cycles or mixture of both. This paper aims at understanding and identifying these different types of dominant structures for reversible as well as nonreversible ergodic Markov processes. Our algorithmic approach generalizes spectral based methods for reversible process by using Schur decomposition techniques which can tackle also nonreversible cases. We illustrate the mathematical construction of our new approach by numerical experiments.}, language = {en} } @article{AbendrothSollederWelkeretal.2015, author = {Abendroth, Frank and Solleder, Marthe and Welker, Pia and Licha, Kai and Weber, Marcus and Seitz, Oliver and Mangoldt, Dorothea}, title = {High affinity flourescence labelled ligands for the estrogen receptor}, volume = {2015}, journal = {Eur. J. Org. Chem.}, number = {10}, pages = {2157 -- 2166}, year = {2015}, language = {en} } @article{WeberZoschkeSedighietal.2014, author = {Weber, Marcus and Zoschke, Christian and Sedighi, Amir and Fleige, Emanuel and Haag, Rainer and Sch{\"a}fer-Korting, Monika}, title = {Free Energy Simulations of Drug loading for Core-Multishell Nanotransporters}, volume = {5}, journal = {J Nanomed Nanotechnol}, number = {5}, doi = {10.4172/2157-7439.1000234}, pages = {234}, year = {2014}, language = {en} } @misc{SteinWeberZoellneretal.2013, author = {Stein, Christoph and Weber, Marcus and Z{\"o}llner, Christian and Scharkoi, Olga}, title = {Fentanyl derivatives as pH-dependent opioid receptor agonists}, journal = {European Patent Application, Bulletin 2013/08}, year = {2013}, language = {en} } @misc{SteinWeberScharkoietal.2013, author = {Stein, Christoph and Weber, Marcus and Scharkoi, Olga and Deuflhard, Peter}, title = {Method and system for identifying compounds that bind and preferably activate a target opioid receptor in a pH-dependent manner}, journal = {European Patent Application, Bulletin 2013/28}, year = {2013}, language = {en} } @article{ZhangWangHartmannetal.2014, author = {Zhang, Wei and Wang, Han and Hartmann, Carsten and Weber, Marcus and Sch{\"u}tte, Christof}, title = {Applications of the cross-entropy method to importance sampling and optimal control of diffusions}, volume = {36}, journal = {Siam Journal on Scientific Computing}, number = {6}, doi = {10.1137/14096493X}, pages = {A2654 -- A2672}, year = {2014}, language = {en} } @article{AndraeMerkelDurmazetal.2014, author = {Andrae, Karsten and Merkel, Stefan and Durmaz, Vedat and Fackeldey, Konstantin and K{\"o}ppen, Robert and Weber, Marcus and Koch, Matthias}, title = {Investigation of the Ergopeptide Epimerization Process}, volume = {2}, journal = {Computation}, number = {3}, doi = {10.3390/computation2030102}, pages = {102 -- 111}, year = {2014}, abstract = {Ergopeptides, like ergocornine and a-ergocryptine, exist in an S- and in an R-configuration. Kinetic experiments imply that certain configurations are preferred depending on the solvent. The experimental methods are explained in this article. Furthermore, computational methods are used to understand this configurational preference. Standard quantum chemical methods can predict the favored configurations by using minimum energy calculations on the potential energy landscape. However, the explicit role of the solvent is not revealed by this type of methods. In order to better understand its influence, classical mechanical molecular simulations are applied. It appears from our research that "folding" the ergopeptide molecules into an intermediate state (between the S- and the R-configuration) is mechanically hindered for the preferred configurations.}, language = {en} } @misc{DeuflhardWeber2014, author = {Deuflhard, Peter and Weber, Marcus}, title = {Mathematics without pain}, volume = {1}, journal = {MATHEON-Mathematics for Key Technologies}, editor = {Deuflhard, Peter and Gr{\"o}tschel, Martin and H{\"o}mberg, Dietmar and Horst, Ulrich and Kramer, J{\"u}rg and Mehrmann, Volker and Polthier, Konrad and Schmidt, Frank and Skutella, Martin and Sprekels, J{\"u}rgen}, publisher = {European Mathematical Society}, doi = {10.4171/137}, pages = {26 -- 28}, year = {2014}, language = {en} } @article{WeberTranfieldHoeoegetal.2014, author = {Weber, Britta and Tranfield, Erin M. and H{\"o}{\"o}g, Johanna L. and Baum, Daniel and Antony, Claude and Hyman, Tony and Verbavatz, Jean-Marc and Prohaska, Steffen}, title = {Automated stitching of microtubule centerlines across serial electron tomograms}, journal = {PLoS ONE}, doi = {10.1371/journal.pone.0113222}, pages = {e113222}, year = {2014}, language = {en} } @misc{RedemannWeberMoelleretal.2014, author = {Redemann, Stefanie and Weber, Britta and M{\"o}ller, Marit and Verbavatz, Jean-Marc and Hyman, Anthony and Baum, Daniel and Prohaska, Steffen and M{\"u}ller-Reichert, Thomas}, title = {The Segmentation of Microtubules in Electron Tomograms Using Amira}, journal = {Mitosis: Methods and Protocols}, publisher = {Springer}, doi = {10.1007/978-1-4939-0329-0_12}, pages = {261 -- 278}, year = {2014}, language = {en} } @article{SchuetteNielsenWeber2015, author = {Sch{\"u}tte, Christof and Nielsen, Adam and Weber, Marcus}, title = {Markov State Models and Molecular Alchemy}, volume = {113}, journal = {Molecular Physics}, number = {1}, doi = {10.1080/00268976.2014.944597}, pages = {69 -- 78}, year = {2015}, abstract = {In recent years Markov State Models (MSMs) have attracted a consid- erable amount of attention with regard to modelling conformation changes and associated function of biomolecular systems. They have been used successfully, e.g., for peptides including time-resolved spectroscopic experiments, protein function and protein folding , DNA and RNA, and ligand-receptor interaction in drug design and more complicated multivalent scenarios. In this article a novel reweighting scheme is introduced that allows to construct an MSM for certain molecular system out of an MSM for a similar system. This permits studying how molecular properties on long timescales differ between similar molecular systems without performing full molecular dynamics simulations for each system under con- sideration. The performance of the reweighting scheme is illustrated for simple test cases including one where the main wells of the respective energy landscapes are located differently and an alchemical transformation of butane to pentane where the dimension of the state space is changed.}, language = {en} } @article{WeberFackeldey2014, author = {Weber, Marcus and Fackeldey, Konstantin}, title = {Computing the Minimal Rebinding Effect Included in a Given Kinetics}, volume = {12}, journal = {Multiscale Model. Simul.}, number = {1}, doi = {10.1137/13091124X}, pages = {318 -- 334}, year = {2014}, abstract = {The rebinding effect is a phenomenon which occurs when observing a ligand-receptor binding process. On the macro scale this process comprises the Markov property. This Makovian view is spoiled when switching to the atomistic scale of a binding process. We therefore suggest a model which accurately describes the rebinding effect on the atomistic scale by allowing ''intermediate'' bound states. This allows us to define an indicator for the magnitude of rebinding and to formulate an optimization problem. The results form our examples show good agreement with data form laboratory.}, language = {en} } @misc{WeberTranfieldHoeoegetal.2014, author = {Weber, Britta and Tranfield, Erin M. and H{\"o}{\"o}g, Johanna L. and Baum, Daniel and Antony, Claude and Hyman, Tony and Verbavatz, Jean-Marc and Prohaska, Steffen}, title = {Automated stitching of microtubule centerlines across serial electron tomograms}, issn = {1438-0064}, doi = {10.1371/journal.pone.0113222}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-52958}, year = {2014}, abstract = {Tracing microtubule centerlines in serial section electron tomography requires microtubules to be stitched across sections, that is lines from different sections need to be aligned, endpoints need to be matched at section boundaries to establish a correspondence between neighboring sections, and corresponding lines need to be connected across multiple sections. We present computational methods for these tasks: 1) An initial alignment is computed using a distance compatibility graph. 2) A fine alignment is then computed with a probabilistic variant of the iterative closest points algorithm, which we extended to handle the orientation of lines by introducing a periodic random variable to the probabilistic formulation. 3) Endpoint correspondence is established by formulating a matching problem in terms of a Markov random field and computing the best matching with belief propagation. Belief propagation is not generally guaranteed to converge to a minimum. We show how convergence can be achieved, nonetheless, with minimal manual input. In addition to stitching microtubule centerlines, the correspondence is also applied to transform and merge the electron tomograms. We applied the proposed methods to samples from the mitotic spindle in C. elegans, the meiotic spindle in X. laevis, and sub-pellicular microtubule arrays in T. brucei. The methods were able to stitch microtubules across section boundaries in good agreement with experts' opinions for the spindle samples. Results, however, were not satisfactory for the microtubule arrays. For certain experiments, such as an analysis of the spindle, the proposed methods can replace manual expert tracing and thus enable the analysis of microtubules over long distances with reasonable manual effort.}, language = {en} } @misc{NielsenWeber2014, author = {Nielsen, Adam and Weber, Marcus}, title = {Computing the nearest reversible Markov chain}, issn = {1438-0064}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-53292}, year = {2014}, abstract = {Reversible Markov chains are the basis of many applications. However, computing transition probabilities by a finite sampling of a Markov chain can lead to truncation errors. Even if the original Markov chain is reversible, the approximated Markov chain might be non-reversible and will lose important properties, like the real valued spectrum. In this paper, we show how to find the closest reversible Markov chain to a given transition matrix. It turns out that this matrix can be computed by solving a convex minimization problem.}, language = {en} } @article{NielsenWeber2015, author = {Nielsen, Adam and Weber, Marcus}, title = {Computing the nearest reversible Markov chain}, volume = {22}, journal = {Numerical Linear Algebra with Applications}, number = {3}, doi = {10.1002/nla.1967}, pages = {483 -- 499}, year = {2015}, abstract = {Reversible Markov chains are the basis of many applications. However, computing transition probabilities by a finite sampling of a Markov chain can lead to truncation errors. Even if the original Markov chain is reversible, the approximated Markov chain might be non-reversible and will lose important properties, like the real valued spectrum. In this paper, we show how to find the closest reversible Markov chain to a given transition matrix. It turns out that this matrix can be computed by solving a convex minimization problem.}, language = {en} }