@inproceedings{SkibinaIliewBethgeetal.2009, author = {Skibina, Julia and Iliew, Rumen and Bethge, Jens and Bock, Martin and Fischer, Dorit and Beloglazov, Valentin and Wedell, Reiner and Burger, Sven and Steinmeyer, G{\"u}nter}, title = {A chirped photonic crystal fiber for high-fidelity guiding of sub-100 fs pluses}, booktitle = {CLEO/QELS}, doi = {10.1364/CLEO.2009.CMHH1}, pages = {CMHH1}, year = {2009}, language = {en} } @incollection{EnkeFiedlerFischeretal.2013, author = {Enke, Harry and Fiedler, Norman and Fischer, Thomas and Gnadt, Timo and Ketzan, Erik and Ludwig, Jens and Rathmann, Torsten and St{\"o}ckle, Gabriel and Schintke, Florian}, title = {Leitfaden zum Forschungsdaten-Management}, booktitle = {Leitfaden zum Forschungsdaten-Management}, editor = {Enke, Harry and Ludwig, Jens}, publisher = {Verlag Werner H{\"u}lsbusch, Gl{\"u}ckstadt}, year = {2013}, language = {en} } @misc{Fischer2016, type = {Master Thesis}, author = {Fischer, Jens}, title = {Evaluating the Scalability of Scalaris}, year = {2016}, language = {en} } @article{FischerCordesSchuette1998, author = {Fischer, Alexander and Cordes, Frank and Sch{\"u}tte, Christof}, title = {Hybrid Monte Carlo with Adaptive Temperature in Mixed-Canonical Ensemble: Efficient conformational analysis of RNA}, volume = {19}, journal = {J. Comp. Chem.}, number = {15}, doi = {10.1002/(SICI)1096-987X(19981130)19:15<1689::AID-JCC2>3.0.CO;2-J}, pages = {1689 -- 1697}, year = {1998}, language = {en} } @inproceedings{FischerSchuetteDeuflhardetal.2002, author = {Fischer, Alexander and Sch{\"u}tte, Christof and Deuflhard, Peter and Cordes, Frank}, title = {Hierarchical Uncoupling-Coupling of Metastable Conformations}, booktitle = {Computational Methods for Macromolecules}, number = {24}, editor = {Schlick, T. and Gan, H.}, publisher = {Springer}, pages = {235 -- 259}, year = {2002}, language = {en} } @article{SchuetteFischerHuisingaetal.1999, author = {Sch{\"u}tte, Christof and Fischer, Alexander and Huisinga, Wilhelm and Deuflhard, Peter}, title = {A Direct Approach to Conformational Dynamics Based on Hybrid Monte Carlo}, volume = {151}, journal = {J. Comput. Phys.}, pages = {146 -- 168}, year = {1999}, language = {en} } @article{BockSkibinaFischeretal.2013, author = {Bock, Martin and Skibina, Julia and Fischer, Dorit and Bretschneider, Mario and Wedell, Reiner and Grunwald, R{\"u}diger and Burger, Sven and Beloglazov, Valentin and Steinmeyer, G{\"u}nter}, title = {Nanostructured fibers for sub-10 fs optical pulse delivery}, volume = {7}, journal = {Laser \& Photonics Reviews}, doi = {10.1002/lpor.201300006}, pages = {566 -- 570}, year = {2013}, language = {en} } @article{DeuflhardHuisingaFischeretal.2000, author = {Deuflhard, Peter and Huisinga, Wilhelm and Fischer, Alexander and Sch{\"u}tte, Christof}, title = {Identification of Almost Invariant Aggregates in Reversible Nearly Uncoupled Markov Chains}, volume = {315}, journal = {Lin. Alg. Appl.}, number = {1-3}, doi = {10.1016/S0024-3795(00)00095-1}, pages = {39 -- 59}, year = {2000}, language = {en} } @article{SchuetteFischerHuisingaetal.1999, author = {Sch{\"u}tte, Christof and Fischer, Alexander and Huisinga, Wilhelm and Deuflhard, Peter}, title = {A Direct Approach to Conformational Dynamics based on Hybrid Monte Carlo}, volume = {151}, journal = {J. Comp. Phys}, number = {1}, doi = {10.1006/jcph.1999.6231}, pages = {146 -- 168}, year = {1999}, language = {en} } @article{FischerCordesSchuette1999, author = {Fischer, Alexander and Cordes, Frank and Sch{\"u}tte, Christof}, title = {Hybrid Monte Carlo with adaptive temperature choice}, volume = {121}, journal = {Comp. Phys. Comm.}, doi = {10.1016/S0010-4655(99)00274-X}, pages = {37 -- 39}, year = {1999}, language = {en} } @article{MeerbachSchuetteFischer2005, author = {Meerbach, E. and Sch{\"u}tte, Christof and Fischer, Alexander}, title = {Eigenvalue Bounds on Restrictions of Reversible Nearly Uncoupled Markov Chains}, volume = {398}, journal = {Lin. Alg. Appl.}, doi = {10.1016/j.laa.2004.10.018}, pages = {141 -- 160}, year = {2005}, language = {en} } @inproceedings{SchuetteForsterMeerbachetal.2005, author = {Sch{\"u}tte, Christof and Forster, R. and Meerbach, E. and Fischer, Alexander}, title = {Uncoupling-Coupling Techniques for Metastable Dynamical Systems}, volume = {40}, booktitle = {Domain Decomposition Methods in Science and Engineering}, editor = {Kornhuber, Ralf and Hoppe, Ronald H. W. and P{\~A}\copyrightriaux, J. and Pironneau, O. and Widlund, Olof and Xu, J.}, publisher = {Springer}, pages = {115 -- 129}, year = {2005}, language = {en} } @article{FischerWaldhausenHorenkoetal.2007, author = {Fischer, Alexander and Waldhausen, S. and Horenko, Illia and Meerbach, E. and Sch{\"u}tte, Christof}, title = {Identification of Biomolecular Conformations from Incomplete Torsion Angle Observations by Hidden Markov Models}, volume = {28}, journal = {J. Comp. Chem.}, number = {15}, doi = {10.1002/jcc.20692}, pages = {2453 -- 2464}, year = {2007}, language = {en} } @article{HorenkoDittmerFischeretal.2006, author = {Horenko, Illia and Dittmer, E. and Fischer, Alexander and Sch{\"u}tte, Christof}, title = {Automated Model Reduction for Complex Systems exhibiting Metastability}, volume = {5}, journal = {Mult. Mod. Sim.}, number = {3}, doi = {10.1137/050623310}, pages = {802 -- 827}, year = {2006}, language = {en} } @article{FischerCordesSchuette1998, author = {Fischer, Alexander and Cordes, Frank and Sch{\"u}tte, Christof}, title = {Hybrid Monte Carlo with adaptive temperature in mixed-canonical ensemble}, volume = {19}, journal = {J. Comp. Chem.}, number = {15}, doi = {10.1002/(SICI)1096-987X(19981130)19:15<1689::AID-JCC2>3.0.CO;2-J}, pages = {1689 -- 1697}, year = {1998}, language = {en} } @inproceedings{FischerSchuetteDeuflhardetal.2002, author = {Fischer, Alexander and Sch{\"u}tte, Christof and Deuflhard, Peter and Cordes, Frank}, title = {Hierarchical Uncoupling-Coupling of Metastable Conformations}, volume = {24}, booktitle = {Computational Methods for Macromolecules}, editor = {Schlick, T. and Gan, H.}, publisher = {Springer}, pages = {235 -- 259}, year = {2002}, language = {en} } @inproceedings{SkibinaIliewBethgeetal.2009, author = {Skibina, Julia and Iliew, Rumen and Bethge, Jens and Bock, Martin and Fischer, Dorit and Beloglazov, Valentin and Wedell, Reiner and Burger, Sven and Steinmeyer, G{\"u}nter}, title = {A chirped photonic crystal fiber for ultrashort laser pulse delivery}, booktitle = {CLEO Europe - EQEC}, doi = {10.1109/CLEOE-EQEC.2009.5196579}, year = {2009}, language = {en} } @article{KramerKreisbeckRihaetal.2016, author = {Kramer, Tobias and Kreisbeck, Christoph and Riha, Christian and Chiatti, Olivio and Buchholz, Sven and Wieck, Andreas and Reuter, Dirk and Fischer, Saskia}, title = {Thermal energy and charge currents in multi-terminal nanorings}, volume = {6}, journal = {AIP Advances}, doi = {10.1063/1.4953812}, pages = {065306}, year = {2016}, abstract = {We study in experiment and theory thermal energy and charge transfer close to the quantum limit in a ballistic nanodevice, consisting of multiply connected one-dimensional electron waveguides. The fabricated device is based on an AlGaAs/GaAs heterostructure and is covered by a global top-gate to steer the thermal energy and charge transfer in the presence of a temperature gradient, which is established by a heating current. The estimate of the heat transfer by means of thermal noise measurements shows the device acting as a switch for charge and thermal energy transfer. The wave-packet simulations are based on the multi-terminal Landauer-B{\"u}ttiker approach and confirm the experimental finding of a mode-dependent redistribution of the thermal energy current, if a scatterer breaks the device symmetry.}, language = {en} } @article{GorgullaBoeszoermnyiWangetal.2020, author = {Gorgulla, Christoph and Boeszoermnyi, Andras and Wang, Zi-Fu and Fischer, Patrick D. and Coote, Paul and Das, Krishna M. Padmanabha and Malets, Yehor S. and Radchenko, Dmytro S. and Moroz, Yurii and Scott, David A. and Fackeldey, Konstantin and Hoffmann, Moritz and Iavniuk, Iryna and Wagner, Gerhard and Arthanari, Haribabu}, title = {An open-source drug discovery platform enables ultra-large virtual screens}, volume = {580}, journal = {Nature}, publisher = {Springer Nature}, doi = {https://doi.org/10.1038/s41586-020-2117-z}, pages = {663 -- 668}, year = {2020}, abstract = {On average, an approved drug today costs \$2-3 billion and takes over ten years to develop1. In part, this is due to expensive and time-consuming wet-lab experiments, poor initial hit compounds, and the high attrition rates in the (pre-)clinical phases. Structure-based virtual screening (SBVS) has the potential to mitigate these problems. With SBVS, the quality of the hits improves with the number of compounds screened2. However, despite the fact that large compound databases exist, the ability to carry out large-scale SBVSs on computer clusters in an accessible, efficient, and flexible manner has remained elusive. Here we designed VirtualFlow, a highly automated and versatile open-source platform with perfect scaling behaviour that is able to prepare and efficiently screen ultra-large ligand libraries of compounds. VirtualFlow is able to use a variety of the most powerful docking programs. Using VirtualFlow, we have prepared the largest and freely available ready-to-dock ligand library available, with over 1.4 billion commercially available molecules. To demonstrate the power of VirtualFlow, we screened over 1 billion compounds and discovered a small molecule inhibitor (iKeap1) that engages KEAP1 with nanomolar affinity (Kd = 114 nM) and disrupts the interaction between KEAP1 and the transcription factor NRF2. We also identified a set of structurally diverse molecules that bind to KEAP1 with submicromolar affinity. This illustrates the potential of VirtualFlow to access vast regions of the chemical space and identify binders with high affinity for target proteins.}, language = {en} } @article{GorgullaDasLeighetal.2021, author = {Gorgulla, Christoph and Das, Krishna M. Padmanabha and Leigh, Kendra E and Cespugli, Marco and Fischer, Patrick D. and Wang, Zi-Fu and Tesseyre, Guilhem and Pandita, Shreya and Shnapir, Alex and Calderaio, Anthony and Hutcheson, Colin and Gechev, Minko and Rose, Alexander and Lewis, Noam and Yaffe, Erez and Luxenburg, Roni and Herce, Henry D. and Durmaz, Vedat and Halazonetis, Thanos D. and Fackeldey, Konstantin and Patten, Justin J. and Chuprina, Alexander and Dziuba, Igor and Plekhova, Alla and Moroz, Yurii and Radchenko, Dmytro and Tarkhanova, Olga and Yavnyuk, Irina and Gruber, Christian C. and Yust, Ryan and Payne, Dave and N{\"a}{\"a}r, Anders M. and Namchuk, Mark N. and Davey, Robert A. and Wagner, Gerhard and Kinney, Jamie and Arthanari, Haribabu}, title = {A Multi-Pronged Approach Targeting SARS-CoV-2 Proteins Using Ultra-Large Virtual Screening}, volume = {24}, journal = {iScience}, number = {2}, publisher = {CellPress}, doi = {10.26434/chemrxiv.12682316}, pages = {102021}, year = {2021}, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), previously known as 2019 novel coronavirus (2019-nCoV), has spread rapidly across the globe, creating an unparalleled global health burden and spurring a deepening economic crisis. As of July 7th, 2020, almost seven months into the outbreak, there are no approved vaccines and few treatments available. Developing drugs that target multiple points in the viral life cycle could serve as a strategy to tackle the current as well as future coronavirus pandemics. Here we leverage the power of our recently developed in silico screening platform, VirtualFlow, to identify inhibitors that target SARS-CoV-2. VirtualFlow is able to efficiently harness the power of computing clusters and cloud-based computing platforms to carry out ultra-large scale virtual screens. In this unprecedented structure-based multi-target virtual screening campaign, we have used VirtualFlow to screen an average of approximately 1 billion molecules against each of 40 different target sites on 17 different potential viral and host targets in the cloud. In addition to targeting the active sites of viral enzymes, we also target critical auxiliary sites such as functionally important protein-protein interaction interfaces. This multi-target approach not only increases the likelihood of finding a potent inhibitor, but could also help identify a collection of anti-coronavirus drugs that would retain efficacy in the face of viral mutation. Drugs belonging to different regimen classes could be combined to develop possible combination therapies, and top hits that bind at highly conserved sites would be potential candidates for further development as coronavirus drugs. Here, we present the top 200 in silico hits for each target site. While in-house experimental validation of some of these compounds is currently underway, we want to make this array of potential inhibitor candidates available to researchers worldwide in consideration of the pressing need for fast-tracked drug development.}, 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} }