@article{FackeldeyNiknejadWeber, author = {Fackeldey, Konstantin and Niknejad, Amir and Weber, Marcus}, title = {Finding Metastabilities in Reversible Markov Chains based on Incomplete Sampling: Case of Molecular Simulation}, series = {Special Matrices}, journal = {Special Matrices}, number = {5/1}, doi = {10.1515/spma-2017-0006}, pages = {73 -- 81}, language = {en} } @article{RaharinirinaFackeldeyWeber, author = {Raharinirina, N. Alexia and Fackeldey, Konstantin and Weber, Marcus}, title = {Qualitative Euclidean embedding of Disjoint Sets of Points}, abstract = {We consider two disjoint sets of points with a distance metric, or a proximity function, associated with each set. If each set can be separately embedded into separate Euclidean spaces, then we provide sufficient conditions for the two sets to be jointly embedded in one Euclidean space. In this joint Euclidean embedding, the distances between the points are generated by a specific relation-preserving function. Consequently, the mutual distances between two points of the same set are specific qualitative transformations of their mutual distances in their original space; the pairwise distances between the points of different sets can be constructed from an arbitrary proximity function (might require scaling).}, language = {en} } @misc{RaharinirinaWeberBirketal., author = {Raharinirina, N. Alexia and Weber, Marcus and Birk, Ralph and Fackeldey, Konstantin and Klasse, Sarah M. and Richter, Tonio Sebastian}, title = {Different Tools and Results for Correspondence Analysis}, doi = {10.12752/8257}, abstract = {This is a list of codes generated from ancient egyptian texts. The codes are used for a correspondence analysis (CA). Codes and CA software are available from the linked webpage.}, language = {en} } @misc{NielsenFackeldeyWeber, author = {Nielsen, Adam and Fackeldey, Konstantin and Weber, Marcus}, title = {On a Generalized Transfer Operator}, issn = {1438-0064}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-43162}, abstract = {We introduce a generalized operator for arbitrary stochastic processes by using a pre-kernel, which is a generalization of the Markov kernel. For deterministic processes, such an operator is already known as the Frobenius-Perron operator, which is defined for a large class of measures. For Markov processes, there exists transfer operators being only well defined for stationary measures in \$L^2\$. Our novel generalized transfer operator is well defined for arbitrary stochastic processes, in particular also for deterministic ones. We can show that this operator is acting on \$L^1\$. For stationary measures, this operator is also an endomorphism of \$L^2\$ and, therefore, allows for a mathematical analysis in Hilbert spaces.}, language = {en} } @misc{KrauseFackeldeyKrause, author = {Krause, Dorian and Fackeldey, Konstantin and Krause, Rolf}, title = {A parallel multiscale simulation toolbox for coupling molecular dynamics and finite elements}, issn = {1438-0064}, doi = {10.1007/978-3-319-00786-1_14}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-42354}, abstract = {It is the ultimate goal of concurrent multiscale methods to provide computational tools that allow to simulation physical processes with the accuracy of micro-scale and the computational speed of macro-scale models. As a matter of fact, the efficient and scalable implementation of concurrent multiscale methods on clusters and supercomputers is a complicated endeavor. In this article we present the parallel multiscale simulation tool MACI which has been designed for efficient coupling between molecular dynamics and finite element codes. We propose a specification for a thin yet versatile interface for the coupling of molecular dynamics and finite element codes in a modular fashion. Further we discuss the parallelization strategy pursued in MACI, in particular, focusing on the parallel assembly of transfer operators and their efficient execution.}, 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}, series = {Applications of Monte Carlo Methods in Biology, Medicine and Other Fields of Science}, booktitle = {Applications of Monte Carlo Methods in Biology, Medicine and Other Fields of Science}, editor = {Mode, Ch.}, publisher = {InTech}, year = {2011}, language = {en} } @article{GorgullaJayarajFackeldeyetal., author = {Gorgulla, Christoph and Jayaraj, Abhilash and Fackeldey, Konstantin and Arthanari, Haribabu}, title = {Emerging frontiers in virtual drug discovery: From quantum mechanical methods to deep learning approaches}, series = {Current Opinion in Chemical Biology}, volume = {69}, journal = {Current Opinion in Chemical Biology}, doi = {10.1016/j.cbpa.2022.102156}, pages = {102156 -- 102156-12}, abstract = {Virtual screening-based approaches to discover initial hit and lead compounds have the potential to reduce both the cost and time of early drug discovery stages, as well as to find inhibitors for even challenging target sites such as protein-protein interfaces. Here in this review, we provide an overview of the progress that has been made in virtual screening methodology and technology on multiple fronts in recent years. The advent of ultra-large virtual screens, in which hundreds of millions to billions of compounds are screened, has proven to be a powerful approach to discover highly potent hit compounds. However, these developments are just the tip of the iceberg, with new technologies and methods emerging to propel the field forward. Examples include novel machine-learning approaches, which can reduce the computational costs of virtual screening dramatically, while progress in quantum-mechanical approaches can increase the accuracy of predictions of various small molecule properties.}, language = {en} } @article{NitzkeFackeldeyVrabec, author = {Nitzke, Isabel and Fackeldey, Konstantin and Vrabec, Jadran}, title = {Long range corrections for inhomogeneous fluids containing a droplet or a bubble}, series = {Molecular Simulation}, journal = {Molecular Simulation}, doi = {https://doi.org/10.1080/08927022.2021.1954639}, pages = {1 -- 14}, abstract = {Long range corrections for molecular simulations of inhomogeneous fluids with a spherical interface are presented. Correction terms for potential energy, force and virial are derived for the monatomic Lennard-Jones fluid. The method is generalised to the Mie potential and arbitrary molecular structures, employing a numerically efficient centre of mass cut-off scheme. The results are validated by a series of droplet simulations for one-centre and two-centre Lennard-Jones fluids with different cut-off radii rc. Systems with rc=8σ provide a check of self-consistence. Further, a system containing a bubble is investigated for the one-centre Lennard-Jones fluid. The equilibrium properties are almost completely independent on the cut-off radius. In comparison with vapour-liquid equilibrium data for systems without a curved interface, all properties show the expected behaviour. Simulation data are used to approximate the surface tension, which is in good agreement with the findings for planar interfaces, thus verifying the present corrections.}, language = {en} } @article{FackeldeyGorgullaWeber, author = {Fackeldey, Konstantin and Gorgulla, Christoph and Weber, Marcus}, title = {Neue Medikamente dank Supercomputern}, series = {Spektrum der Wissenschaft}, journal = {Spektrum der Wissenschaft}, number = {11}, pages = {40 -- 46}, abstract = {Die aktuelle Pandemie verdeutlicht, wie wichtig es ist, rasch geeignete Arzneimittel zu finden. In Computer­simulationen gelingt das erheblich schneller als im Labor. Gegen das Coronavirus ließen sich auf diese Weise bereits Wirkstoffkandidaten identifizieren.}, language = {de} } @misc{LieFackeldeyWeber, author = {Lie, Han Cheng and Fackeldey, Konstantin and Weber, Marcus}, title = {A square root approximation of transition rates for a Markov State Model}, issn = {1438-0064}, doi = {10.1137/120899959}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-42195}, abstract = {Trajectory- or mesh-based methods for analyzing the dynamical behavior of large molecules tend to be impractical due to the curse of dimensionality - their computational cost increases exponentially with the size of the molecule. We propose a method to break the curse by a novel square root approximation of transition rates, Monte Carlo quadrature and a discretization approach based on solving linear programs. With randomly sampled points on the molecular energy landscape and randomly generated discretizations of the molecular configuration space as our initial data, we construct a matrix describing the transition rates between adjacent discretization regions. This transition rate matrix yields a Markov State Model of the molecular dynamics. We use Perron cluster analysis and coarse-graining techniques in order to identify metastable sets in configuration space and approximate the transition rates between the metastable sets. Application of our method to a simple energy landscape on a two-dimensional configuration space provides proof of concept and an example for which we compare the performance of different discretizations. We show that the computational cost of our method grows only polynomially with the size of the molecule. However, finding discretizations of higher-dimensional configuration spaces in which metastable sets can be identified remains a challenge.}, language = {en} } @misc{FackeldeyKoltaiNeviretal., author = {Fackeldey, Konstantin and Koltai, P{\´e}ter and N{\´e}vir, Peter and Rust, Henning and Schild, Axel and Weber, Marcus}, title = {From Metastable to Coherent Sets - time-discretization schemes}, issn = {1438-0064}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-66074}, abstract = {Given a time-dependent stochastic process with trajectories x(t) in a space \$\Omega\$, there may be sets such that the corresponding trajectories only very rarely cross the boundaries of these sets. We can analyze such a process in terms of metastability or coherence. Metastable sets M are defined in space \$M\subset\Omega\$, coherent sets \$M(t)\subset\Omega\$ are defined in space and time. Hence, if we extend the space by the time-variable t, coherent sets are metastable sets in \$\Omega\times[0,\infty]\$. This relation can be exploited, because there already exist spectral algorithms for the identification of metastable sets. In this article we show that these well-established spectral algorithms (like PCCA+) also identify coherent sets of non-autonomous dynamical systems. For the identification of coherent sets, one has to compute a discretization (a matrix T) of the transfer operator of the process using a space-timediscretization scheme. The article gives an overview about different time-discretization schemes and shows their applicability in two different fields of application.}, 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}, series = {Journal of Chemical Theory and Computation}, 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} } @misc{WeberFackeldeySchuette, author = {Weber, Marcus and Fackeldey, Konstantin and Sch{\"u}tte, Christof}, title = {Set-free Markov State Building}, issn = {1438-0064}, doi = {10.1063/1.4978501}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-62167}, abstract = {Molecular dynamics (MD) simulations face challenging problems since the timescales of interest often are much longer than what is possible to simulate and even if sufficiently long simulation are possible the complex nature of the resulting simulation data makes interpretation difficult. Markov State Models (MSMs) help to overcome these problems by making experimentally relevant timescales accessible via coarse grained representations that also allows for convenient interpretation. However, standard set-based MSMs exhibit some caveats limiting their approximation quality and statistical significance. One of the main caveats results from the fact that typical MD trajectories repeatedly re-cross the boundary between the sets used to build the MSM which causes statistical bias in estimating the transition probabilities between these sets. In this article, we present a set-free approach to MSM building utilizing smooth overlapping ansatz functions instead of sets and an adaptive refinement approach. This kind of meshless discretization helps to overcome the recrossing problem and yields an adaptive refinement procedure that allows to improve the quality of the model while exploring state space and inserting new ansatz functions into the MSM.}, language = {en} } @inproceedings{FackeldeyKrauseSchweitzer2008, author = {Fackeldey, Konstantin and Krause, Rolf and Schweitzer, M.}, title = {Stability of Energy Transfer in the Weak Coupling Method}, series = {Meshfree Methods for Partial Differential Equations IV}, volume = {65}, booktitle = {Meshfree Methods for Partial Differential Equations IV}, editor = {Griebel, Michael and Schweitzer, M.}, pages = {111 -- 121}, year = {2008}, language = {en} } @article{FackeldeyKrause2009, author = {Fackeldey, Konstantin and Krause, Rolf}, title = {Multiscale Coupling in Function Space - Weak Coupling between Molecular Dynamics and Continuum Mechanics}, series = {International Journal for Numerical Methods in Engineering}, volume = {79}, journal = {International Journal for Numerical Methods in Engineering}, number = {12}, doi = {10.1002/nme.2626}, pages = {1517 -- 1535}, year = {2009}, language = {en} } @article{FackeldeyKrauseKrauseetal.2011, author = {Fackeldey, Konstantin and Krause, Dorian and Krause, Rolf and Lenzen, Christoph}, title = {Coupling Molecular Dynamics and Continua with Weak Constraints}, series = {SIAM Multiscale Model. Simul.}, volume = {9}, journal = {SIAM Multiscale Model. Simul.}, doi = {/10.1137/100782097}, pages = {1459 -- 1494}, year = {2011}, language = {en} } @inproceedings{FackeldeyKrause2007, author = {Fackeldey, Konstantin and Krause, Rolf}, title = {Solving Frictional Contact Problems with Multigrid Efficiency}, series = {Proc.of the 16th International Conference on Domain Decomposition Methods}, volume = {50}, booktitle = {Proc.of the 16th International Conference on Domain Decomposition Methods}, editor = {Widlund, Olof}, pages = {547 -- 554}, year = {2007}, language = {en} } @inproceedings{FackeldeyKrauseKrause2010, author = {Fackeldey, Konstantin and Krause, Dorian and Krause, Rolf}, title = {Numerical Validation of Constraints Based Multiscale Methods}, series = {Lecture Notes in Computational Science and Engineering}, booktitle = {Lecture Notes in Computational Science and Engineering}, editor = {Griebel, Michael and Schweitzer, M.}, pages = {141 -- 154}, year = {2010}, language = {en} } @inproceedings{FackeldeyKrauseKrause2008, author = {Fackeldey, Konstantin and Krause, Dorian and Krause, Rolf}, title = {Quadrature and Implementation of the Weak Coupling Method}, series = {MMM 2008: Proceedings of the 4th International Conference on Multiscale Materials Modelling, 27-31 October 2008, Tallahassee, Fla.}, booktitle = {MMM 2008: Proceedings of the 4th International Conference on Multiscale Materials Modelling, 27-31 October 2008, Tallahassee, Fla.}, pages = {62 -- 65}, year = {2008}, language = {en} } @inproceedings{FackeldeyKrauseKrause2009, author = {Fackeldey, Konstantin and Krause, Dorian and Krause, Rolf}, title = {Weak Coupling Algorithms in Multiscale Simulations}, series = {Proceedings of the third Inter. Confer. on Comp. Meth. for Coupled Problems in Science and Engrg}, booktitle = {Proceedings of the third Inter. Confer. on Comp. Meth. for Coupled Problems in Science and Engrg}, pages = {1023pp}, year = {2009}, language = {en} } @inproceedings{FackeldeyKrause2008, author = {Fackeldey, Konstantin and Krause, Rolf}, title = {CM/MD Coupling - A Function Space Oriented Multiscale-Coupling Approach}, series = {Proc. Appl. Math. Mech.}, volume = {8}, booktitle = {Proc. Appl. Math. Mech.}, number = {1}, pages = {10495pp}, year = {2008}, language = {en} } @phdthesis{Fackeldey2009, author = {Fackeldey, Konstantin}, title = {The Weak Coupling Method for Coupling Continuum Mechanics with Molecular Dynamics}, year = {2009}, language = {en} } @inproceedings{FackeldeyKrause2007, author = {Fackeldey, Konstantin and Krause, Rolf}, title = {Weak coupling in function space}, series = {Proc. Appl. Math. Mech.}, volume = {7}, booktitle = {Proc. Appl. Math. Mech.}, number = {1}, pages = {2020113pp}, year = {2007}, language = {en} } @article{KrauseFackeldeyKrause2014, author = {Krause, Dorian and Fackeldey, Konstantin and Krause, Rolf}, title = {A Parallel Multiscale Simulation Toolbox for Coupling Molecular Dynamics and Finite Elements}, series = {Singular Phenomena and Scaling in Mathematical Models}, journal = {Singular Phenomena and Scaling in Mathematical Models}, editor = {Griebel, Michael}, publisher = {Springer International Publishing}, doi = {10.1007/978-3-319-00786-1_14}, pages = {327 -- 346}, year = {2014}, language = {en} } @article{Fackeldey2011, author = {Fackeldey, Konstantin}, title = {Coupling Meshbased and Meshfree Methods by a Transfer Operator Approach}, series = {IJPAM}, volume = {69}, journal = {IJPAM}, number = {2}, pages = {185 -- 202}, year = {2011}, language = {en} } @inproceedings{Fackeldey2012, author = {Fackeldey, Konstantin}, title = {Multiscale Methods in Time and Space}, series = {Progress in Industrial Mathematics at ECMI 2010}, volume = {17}, booktitle = {Progress in Industrial Mathematics at ECMI 2010}, pages = {619 -- 626}, year = {2012}, language = {en} } @misc{Fackeldey, author = {Fackeldey, Konstantin}, title = {Challenges in Atomistic-to-Continuum Coupling}, series = {ZIB Report}, volume = {2010}, journal = {ZIB Report}, edition = {10-12}, doi = {10.1155/2015/834517}, abstract = {This paper is concerned with the design, analysis, and implementation of concurrent coupling approaches where different (atomic and continuous) models are used simultaneously within a single simulation process. Thereby, several problems or pitfalls can happen, for example, the reflection of molecular movements at the "boundary" between the atomic and continuum regions which leads to an unphysical increase in energy in the atomic model. We investigate the problems with the aim of giving an introduction into this field and preventing errors for scientists starting their research towards multiscale methods.}, language = {en} } @article{FackeldeyWeber, author = {Fackeldey, Konstantin and Weber, Marcus}, title = {GenPCCA -- Markov State Models for Non-Equilibrium Steady States}, series = {Big data clustering: Data preprocessing, variable selection, and dimension reduction. WIAS Report No. 29}, journal = {Big data clustering: Data preprocessing, variable selection, and dimension reduction. WIAS Report No. 29}, doi = {10.20347/WIAS.REPORT.29}, pages = {70 -- 80}, language = {en} } @article{AndraeMerkelDurmazetal., 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}, series = {Computation}, volume = {2}, journal = {Computation}, number = {3}, doi = {10.3390/computation2030102}, pages = {102 -- 111}, 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} } @article{AndraeDurmazFackeldeyetal., author = {Andrae, Karsten and Durmaz, Vedat and Fackeldey, Konstantin and Scharkoi, Olga and Weber, Marcus}, title = {Medizin aus dem Computer}, series = {Der Anaesthesist}, volume = {62}, journal = {Der Anaesthesist}, number = {7}, publisher = {Springer}, doi = {10.1007/s00101-013-2202-x}, pages = {561 -- 557}, language = {de} } @article{ScharkoiFackeldeyMerkulowetal.2013, author = {Scharkoi, Olga and Fackeldey, Konstantin and Merkulow, Igor and Andrae, Karsten and Weber, Marcus and Nehls, Irene}, title = {Conformational Analysis of Alternariol on the Quantum Level}, series = {J. Mol. Model.}, volume = {19}, journal = {J. Mol. Model.}, number = {6}, doi = {10.1007/s00894-013-1803-2}, pages = {2567 -- 2572}, year = {2013}, language = {en} } @article{BirkRaharinirinaFackeldeyetal., author = {Birk, Ralph and Raharinirina, N. Alexia and Fackeldey, Konstantin and Richter, Tonio Sebastian and Weber, Marcus}, title = {Inferring cultural and social processes based on patterns of statistical relationships between Synodal texts}, abstract = {In this paper, we explore the relationship patterns between Ancient Egyptian texts of the corpus ``Synodal decrees'', which are originating between 243 and 185 BCE, during the Ptolemaic period. Particularly, we are interested in analyzing the grammatical features of the different texts. Conventional data analysis methods such as correspondence Analysis are very useful to explore the patterns of statistical interdependence between categories of variables. However, it is based on a PCA-like dimension-reduction method and turned out to be unsuitable for our dataset due to the high dimensionality of our data representations. Additionally, the similarity between pairs of texts and pairs of grammatical features is observed through the distance between their representation, but the degree of association between a particular grammatical feature and a text is not. Here, we applied a qualitative Euclidean embedding method that provides a new Euclidean representation of the categories of variables. This new representation of the categories is constructed in such a way that all the patterns of statistical interdependence, similarity, and association, are seen through the Euclidean distance between them. Nevertheless, the PCA-like dimension-reduction method also performed poorly on our new representation. Therefore, we obtained a two-dimensional visualization using non-linear methods such UMAP or t-SNE. Although these dimension-reduction methods reduced the interpretability of interpoint distances, we were still able to identify important similarity patterns between the Synodal text as well as their association patterns with the grammatical features.}, language = {en} } @article{RayFackeldeySteinetal., author = {Ray, Sourav and Fackeldey, Konstantin and Stein, Christoph and Weber, Marcus}, title = {Coarse Grained MD Simulations of Opioid interactions with the µ-opioid receptor and the surrounding lipid membrane}, series = {Biophysica}, volume = {3}, journal = {Biophysica}, number = {2}, doi = {10.3390/biophysica3020017}, pages = {263 -- 275}, abstract = {In our previous studies, a new opioid (NFEPP) was developed to only selectively bind to the 𝜇-opoid receptor (MOR) in inflamed tissue and thus avoid the severe side effects of fentanyl. We know that NFEPP has a reduced binding affinity to MOR in healthy tissue. Inspired by the modelling and simulations performed by Sutcliffe et al., we present our own results of coarse-grained molecular dynamics simulations of fentanyl and NFEPP with regards to their interaction with the 𝜇-opioid receptor embedded within the lipid cell membrane. For technical reasons, we have slightly modified Sutcliffe's parametrisation of opioids. The pH-dependent opioid simulations are of interest because while fentanyl is protonated at the physiological pH, NFEPP is deprotonated due to its lower pKa value than that of fentanyl. Here, we analyse for the first time whether pH changes have an effect on the dynamical behaviour of NFEPP when it is inside the cell membrane. Besides these changes, our analysis shows a possible alternative interaction of NFEPP at pH 7.4 outside the binding region of the MOR. The interaction potential of NFEPP with MOR is also depicted by analysing the provided statistical molecular dynamics simulations with the aid of an eigenvector analysis of a transition rate matrix. In our modelling, we see differences in the XY-diffusion profiles of NFEPP compared with fentanyl in the cell membrane.}, language = {en} } @article{DonatiFackeldeyWeber2023, author = {Donati, Luca and Fackeldey, Konstantin and Weber, Marcus}, title = {Augmented ant colony algorithm for virtual drug discovery}, series = {Journal of Mathematical Chemistry}, volume = {62}, journal = {Journal of Mathematical Chemistry}, doi = {10.1007/s10910-023-01549-6}, pages = {367 -- 385}, year = {2023}, abstract = {Docking is a fundamental problem in computational biology and drug discovery that seeks to predict a ligand's binding mode and affinity to a target protein. However, the large search space size and the complexity of the underlying physical interactions make docking a challenging task. Here, we review a docking method, based on the ant colony optimization algorithm, that ranks a set of candidate ligands by solving a minimization problem for each ligand individually. In addition, we propose an augmented version that takes into account all energy functions collectively, allowing only one minimization problem to be solved. The results show that our modification outperforms in accuracy and efficiency.}, language = {en} } @article{SchimunekSeidlElezetal.2023, author = {Schimunek, Johannes and Seidl, Philipp and Elez, Katarina and Hempel, Tim and Le, Tuan and No{\´e}, Frank and Olsson, Simon and Raich, Llu{\´i}s and Winter, Robin and Gokcan, Hatice and Gusev, Filipp and Gutkin, Evgeny M. and Isayev, Olexandr and Kurnikova, Maria G. and Narangoda, Chamali H. and Zubatyuk, Roman and Bosko, Ivan P. and Furs, Konstantin V. and Karpenko, Anna D. and Kornoushenko, Yury V. and Shuldau, Mikita and Yushkevich, Artsemi and Benabderrahmane, Mohammed B. and Bousquet-Melou, Patrick and Bureau, Ronan and Charton, Beatrice and Cirou, Bertrand C. and Gil, G{\´e}rard and Allen, William J. and Sirimulla, Suman and Watowich, Stanley and Antonopoulos, Nick and Epitropakis, Nikolaos and Krasoulis, Agamemnon and Itsikalis, Vassilis and Theodorakis, Stavros and Kozlovskii, Igor and Maliutin, Anton and Medvedev, Alexander and Popov, Petr and Zaretckii, Mark and Eghbal-Zadeh, Hamid and Halmich, Christina and Hochreiter, Sepp and Mayr, Andreas and Ruch, Peter and Widrich, Michael and Berenger, Francois and Kumar, Ashutosh and Yamanishi, Yoshihiro and Zhang, Kam Y. J. and Bengio, Emmanuel and Bengio, Yoshua and Jain, Moksh J. and Korablyov, Maksym and Liu, Cheng-Hao and Marcou, Gilles and Glaab, Enrico and Barnsley, Kelly and Iyengar, Suhasini M. and Ondrechen, Mary Jo and Haupt, V. Joachim and Kaiser, Florian and Schroeder, Michael and Pugliese, Luisa and Albani, Simone and Athanasiou, Christina and Beccari, Andrea and Carloni, Paolo and D'Arrigo, Giulia and Gianquinto, Eleonora and Goßen, Jonas and Hanke, Anton and Joseph, Benjamin P. and Kokh, Daria B. and Kovachka, Sandra and Manelfi, Candida and Mukherjee, Goutam and Mu{\~n}iz-Chicharro, Abraham and Musiani, Francesco and Nunes-Alves, Ariane and Paiardi, Giulia and Rossetti, Giulia and Sadiq, S. Kashif and Spyrakis, Francesca and Talarico, Carmine and Tsengenes, Alexandros and Wade, Rebecca C. and Copeland, Conner and Gaiser, Jeremiah and Olson, Daniel R. and Roy, Amitava and Venkatraman, Vishwesh and Wheeler, Travis J. and Arthanari, Haribabu and Blaschitz, Klara and Cespugli, Marco and Durmaz, Vedat and Fackeldey, Konstantin and Fischer, Patrick D. and Gorgulla, Christoph and Gruber, Christian and Gruber, Karl and Hetmann, Michael and Kinney, Jamie E. and Padmanabha Das, Krishna M. and Pandita, Shreya and Singh, Amit and Steinkellner, Georg and Tesseyre, Guilhem and Wagner, Gerhard and Wang, Zi-Fu and Yust, Ryan J. and Druzhilovskiy, Dmitry S. and Filimonov, Dmitry A. and Pogodin, Pavel V. and Poroikov, Vladimir and Rudik, Anastassia V. and Stolbov, Leonid A. and Veselovsky, Alexander V. and De Rosa, Maria and De Simone, Giada and Gulotta, Maria R. and Lombino, Jessica and Mekni, Nedra and Perricone, Ugo and Casini, Arturo and Embree, Amanda and Gordon, D. Benjamin and Lei, David and Pratt, Katelin and Voigt, Christopher A. and Chen, Kuang-Yu and Jacob, Yves and Krischuns, Tim and Lafaye, Pierre and Zettor, Agn{\`e}s and Rodr{\´i}guez, M. Luis and White, Kris M. and Fearon, Daren and Von Delft, Frank and Walsh, Martin A. and Horvath, Dragos and Brooks III, Charles L. and Falsafi, Babak and Ford, Bryan and Garc{\´i}a-Sastre, Adolfo and Yup Lee, Sang and Naffakh, Nadia and Varnek, Alexandre and Klambauer, G{\"u}nter and Hermans, Thomas M.}, title = {A community effort in SARS-CoV-2 drug discovery}, series = {Molecular Informatics}, volume = {43}, journal = {Molecular Informatics}, number = {1}, doi = {https://doi.org/10.1002/minf.202300262}, pages = {e202300262}, year = {2023}, language = {en} } @misc{Secker, author = {Secker, Christopher}, title = {Novel multi-objective affinity approach allows to identify pH-specific μ-opioid receptor agonists (Dataset)}, doi = {10.12752/9622}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-96220}, abstract = {Virtual Screening Dataset for the paper "Novel multi-objective affinity approach allows to identify pH-specific μ-opioid receptor agonists" by Secker et al. (https://doi.org/10.1186/s13321-023-00746-4)}, language = {en} } @article{SeckerFackeldeyWeberetal., author = {Secker, Christopher and Fackeldey, Konstantin and Weber, Marcus and Ray, Sourav and Gorgulla, Christoph and Sch{\"u}tte, Christof}, title = {Novel multi-objective affinity approach allows to identify pH-specific μ-opioid receptor agonists}, series = {Journal of Cheminformatics}, volume = {15}, journal = {Journal of Cheminformatics}, doi = {10.1186/s13321-023-00746-4}, abstract = {Opioids are essential pharmaceuticals due to their analgesic properties, however, lethal side effects, addiction, and opioid tolerance are extremely challenging. The development of novel molecules targeting the μ-opioid receptor (MOR) in inflamed, but not in healthy tissue, could significantly reduce these unwanted effects. Finding such novel molecules can be achieved by maximizing the binding affinity to the MOR at acidic pH while minimizing it at neutral pH, thus combining two conflicting objectives. Here, this multi-objective optimal affinity approach is presented, together with a virtual drug discovery pipeline for its practical implementation. When applied to finding pH-specific drug candidates, it combines protonation state-dependent structure and ligand preparation with high-throughput virtual screening. We employ this pipeline to characterize a set of MOR agonists identifying a morphine-like opioid derivative with higher predicted binding affinities to the MOR at low pH compared to neutral pH. Our results also confirm existing experimental evidence that NFEPP, a previously described fentanyl derivative with reduced side effects, and recently reported β-fluorofentanyls and -morphines show an increased specificity for the MOR at acidic pH when compared to fentanyl and morphine. We further applied our approach to screen a >50K ligand library identifying novel molecules with pH-specific predicted binding affinities to the MOR. The presented differential docking pipeline can be applied to perform multi-objective affinity optimization to identify safer and more specific drug candidates at large scale.}, language = {en} } @article{RaharinirinaSunkaravonKleistetal., author = {Raharinirina, Nomenjanahary Alexia and Sunkara, Vikram and von Kleist, Max and Fackeldey, Konstantin and Weber, Marcus}, title = {Multi-Input data ASsembly for joint Analysis (MIASA): A framework for the joint analysis of disjoint sets of variables}, series = {PLOS ONE}, volume = {19}, journal = {PLOS ONE}, number = {5}, publisher = {Public Library of Science}, doi = {10.1371/journal.pone.0302425}, pages = {26}, language = {en} } @article{GorgullaNigamKoopetal., author = {Gorgulla, Christoph and Nigam, AkshatKumar and Koop, Matt and Selim {\c{C}}{\i}naroğlu, S{\"u}leyman and Secker, Christopher and Haddadnia, Mohammad and Kumar, Abhishek and Malets, Yehor and Hasson, Alexander and Li, Minkai and Tang, Ming and Levin-Konigsberg, Roni and Radchenko, Dmitry and Kumar, Aditya and Gehev, Minko and Aquilanti, Pierre-Yves and Gabb, Henry and Alhossary, Amr and Wagner, Gerhard and Aspuru-Guzik, Al{\´a}n and Moroz, Yurii S. and Fackeldey, Konstantin and Arthanari, Haribabu}, title = {VirtualFlow 2.0 - The Next Generation Drug Discovery Platform Enabling Adaptive Screens of 69 Billion Molecules}, series = {bioRxiv}, journal = {bioRxiv}, doi = {10.1101/2023.04.25.537981}, language = {en} }