@misc{GalliatDeuflhardRoitzschetal., author = {Galliat, Tobias and Deuflhard, Peter and Roitzsch, Rainer and Cordes, Frank}, title = {Automatic Identification of Metastable Conformations via Self-Organized Neural Networks}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-6197}, number = {00-51}, abstract = {As has been shown recently, the identification of metastable chemical conformations leads to a Perron cluster eigenvalue problem for a reversible Markov operator. Naive discretization of this operator would suffer from combinatorial explosion. As a first remedy, a pre-identification of essential degrees of freedom out of the set of torsion angles had been applied up to now. The present paper suggests a different approach based on neural networks: its idea is to discretize the Markov operator via self-organizing (box) maps. The thus obtained box discretization then serves as a prerequisite for the subsequent Perron cluster analysis. Moreover, this approach also permits exploitation of additional structure within embedded simulations. As it turns out, the new method is fully automatic and efficient also in the treatment of biomolecules. This is exemplified by numerical results.}, language = {en} } @misc{CordesWeberSchmidtEhrenberg, 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}, 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{BaumeisterCordes, author = {Baumeister, Timm and Cordes, Frank}, title = {A new Model for the Free Energy of Solvation and its Application in Protein Ligand Scoring}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-8265}, number = {04-51}, abstract = {A new and time efficient model to evaluate the free energy of solvation has been developed. The solvation free energy is separated into an electrostatic term, a hydrogen bond term, and a rest-term, combining both entropic and van der Waals effects. The electrostatic contribution is evaluated with a simplified boundary element method using the partial charges of the MMFF94 force field. The number of hydrogen bonds and the solvent excluded surface area over the surface atoms are used in a linear model to estimate the non-electrostatic contribution. This model is applied to a set of 213 small and mostly organic molecules, yielding an rmsd of 0.87kcal/mol and a correlation with experimental data of r=0.951. The model is applied as a supplementary component of the free energy of binding to estimate binding constants of protein ligand complexes. The intermolecular interaction energy is evaluated by using the MMFF94 force field.}, language = {en} } @misc{MayEisenhardtSchmidtEhrenbergetal., author = {May, Andreas and Eisenhardt, Steffen and Schmidt-Ehrenberg, Johannes and Cordes, Frank}, title = {Rigid body docking for Virtual Screening}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-7690}, number = {03-47}, abstract = {A recently developed algorithm allows Rigid Body Docking of ligands to proteins, regardless of the accessibility and location of the binding site. The Docking procedure is divided into three subsequent optimization phases, two of which utilize rigid body dynamics. The last one is applied with the ligand already positioned inside the binding pocket and accounts for full flexibility. Initially, a combination of geometrical and force-field based methods is used as a Coarse Docking strategy, considering only Lennard-Jones interactions between the target and pharmaceutically relevant atoms or functional groups. The protein is subjected to a Hot Spot Analysis, which reveals points of high affinity in the protein environment towards these groups. The hot spots are distributed into different subsets according to their group affiliation. The ligand is described as a complementary point set, consisting of the same subsets. Both sets are matched in \$\mathrm{I\!R}^{3}\$, by superimposing members of the same subsets. In the first instance, steric inhibition is nearly neglected, preventing the system's trajectory from trapping in local minima and thus from finding false positive solutions. Hence the exact location of the binding site can be determined fast and reliably without any additional information. Subsequently, errors resulting from approximations are minimized via finetuning, this time considering both Lennard-Jones and Coulomb forces. Finally, the potential energy of the whole complex is minimized. In a first evaluation, results are rated by a reduced scoring function considering only noncovalent interaction energies. Exemplary Screening results will be given for specific ligands.}, language = {en} } @misc{BoitCordes, author = {Boit, Alice and Cordes, Frank}, title = {RNA 3D-Modeling}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-7708}, number = {03-48}, abstract = {This article presents a new computational approach to the three-dimensional (3D) modeling of ribonucleic acid (RNA) sequences with unknown spatial structure. The main concept is a mapping of the query sequence onto the 3D structures of a suitable template RNA molecule. This technique called \textit{threading} has originally been developed for the modeling of protein 3D structures. The application to RNA systems bridges the information gap between the growing mass of RNA sequence data and the relatively limited number of available 3D structures. The new RNA threading method is demonstrated on a tRNA model system because sufficient representative 3D structures have experimentally been elucidated and deposited in the public databases. Nevertheless, the method is in principle transferable on all other RNA species. Algorithms are developed that decompose these template structures into their secondary structure elements and gather this information in a specific template database. The best template is chosen with public alignment and secondary structure prediction tools which are integrated in the RNA modeling module. The structural information gathered from the template and the best alignment is combined to establish a comprehensive 3D model of the query sequence. A range of complete tRNA structures has successfully been modeled with the RNA threading method. The prototype module visualizes the models and provides convenient access to the proposed 3D structures. Therefore, the method could give new insight into a variety of RNA systems which in the recent years have become increasingly important as potential new pharmaceutical agents.}, language = {en} } @misc{MeyerMollCordesetal., author = {Meyer, Holger and Moll, Sebastian and Cordes, Frank and Weber, Marcus}, title = {ConFlow? A new space-based Application for complete Conformational Analysis of Molecules}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-9258}, number = {06-31}, abstract = {Biochemical interactions are determined by the 3D-structure of the involved components - thus the identification of conformations is a key for many applications in rational drug design. {\sf ConFlow} is a new multilevel approach to conformational analysis with main focus on completeness in investigation of conformational space. In contrast to known conformational analysis, the starting point for design is a space-based description of conformational areas. A tight integration of sampling and analysis leads to an identification of conformational areas simultaneously during sampling. An incremental decomposition of high-dimensional conformational space is used to guide the analysis. A new concept for the description of conformations and their path connected components based on convex hulls and {\em Hypercubes}is developed. The first results of the {\sf ConFlow} application constitute a 'proof of concept' and are further more highly encouraging. In comparison to conventional industrial applications, {\sf ConFlow} achieves higher accuracy and a specified degree of completeness with comparable effort.}, language = {en} } @misc{HuisingaBestCordesetal., author = {Huisinga, Wilhelm and Best, Christoph and Cordes, Frank and Roitzsch, Rainer and Sch{\"u}tte, Christof}, title = {From Simulation Data to Conformational Ensembles: Structure and Dynamics based Methods}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-3797}, number = {SC-98-36}, abstract = {Statistical methods for analyzing large data sets of molecular configurations within the chemical concept of molecular conformations are described. The strategies are based on dependencies between configurations of a molecular ensemble; the article concentrates on dependencies induces by a) correlations between the molecular degrees of freedom, b) geometrical similarities of configurations, and c) dynamical relations between subsets of configurations. The statistical technique realizing aspect a) is based on an approach suggested by {\sc Amadei et al.} (Proteins, 17 (1993)). It allows to identify essential degrees of freedom of a molecular system and is extended in order to determine single configurations as representatives for the crucial features related to these essential degrees of freedom. Aspects b) and c) are based on statistical cluster methods. They lead to a decomposition of the available simulation data into {\em conformational ensembles} or {\em subsets} with the property that all configurations in one of these subsets share a common chemical property. In contrast to the restriction to single representative conformations, conformational ensembles include information about, e.g., structural flexibility or dynamical connectivity. The conceptual similarities and differences of the three approaches are discussed in detail and are illustrated by application to simulation data originating from a hybrid Monte Carlo sampling of a triribonucleotide.}, language = {en} } @misc{FischerCordesSchuette, author = {Fischer, Alexander and Cordes, Frank and Sch{\"u}tte, Christof}, title = {Hybrid Monte Carlo with Adaptive Temperature in a Mixed-Canonical Ensemble: Efficient Conformational Analysis of RNA}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-3364}, number = {SC-97-67}, abstract = {A hybrid Monte Carlo method with adaptive temperature choice is presented, which exactly generates the distribution of a mixed-canonical ensemble composed of two canonical ensembles at low and high temperature. The analysis of resulting Markov chains with the reweighting technique shows an efficient sampling of the canonical distribution at low temperature, whereas the high temperature component facilitates conformational transitions, which allows shorter simulation times. \\The algorithm was tested by comparing analytical and numerical results for the small n-butane molecule before simulations were performed for a triribonucleotide. Sampling the complex multi-minima energy landscape of these small RNA segments, we observed enforced crossing of energy barriers.}, language = {en} } @misc{FischerSchuetteDeuflhardetal., author = {Fischer, Alexander and Sch{\"u}tte, Christof and Deuflhard, Peter and Cordes, Frank}, title = {Hierarchical Uncoupling-Coupling of Metastable Conformations}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-6296}, number = {01-03}, abstract = {Uncoupling-coupling Monte Carlo (UCMC) combines uncoupling techniques for finite Markov chains with Markov chain Monte Carlo methodology. UCMC aims at avoiding the typical metastable or trapping behavior of Monte Carlo techniques. From the viewpoint of Monte Carlo, a slowly converging long-time Markov chain is replaced by a limited number of rapidly mixing short-time ones. Therefore, the state space of the chain has to be hierarchically decomposed into its metastable conformations. This is done by means of combining the technique of conformation analysis as recently introduced by the authors, and appropriate annealing strategies. We present a detailed examination of the uncoupling-coupling procedure which uncovers its theoretical background, and illustrates the hierarchical algorithmic approach. Furthermore, application of the UCMC algorithm to the \$n\$-pentane molecule allows us to discuss the effect of its crucial steps in a typical molecular scenario.}, 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}, series = {J. Comp. Chem.}, 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}, series = {Computational Methods for Macromolecules}, booktitle = {Computational Methods for Macromolecules}, number = {24}, editor = {Schlick, T. and Gan, H.}, publisher = {Springer}, pages = {235 -- 259}, year = {2002}, language = {en} } @inproceedings{GalliatDeuflhardRoitzschetal.2002, author = {Galliat, Tobias and Deuflhard, Peter and Roitzsch, Rainer and Cordes, Frank}, title = {Automatic identification of metastable conformations via self-organized neural networks}, series = {Proceedings of the 3rd International Workshop on Algorithms for Macromolecular Modelling}, booktitle = {Proceedings of the 3rd International Workshop on Algorithms for Macromolecular Modelling}, year = {2002}, language = {en} } @inproceedings{GalliatDeuflhardRoitzschetal.2002, author = {Galliat, Tobias and Deuflhard, Peter and Roitzsch, Rainer and Cordes, Frank}, title = {Automatic Identification of Metastable Conformations via Self-Organized Neural Networks}, series = {Computational Methods for Macromolecules}, booktitle = {Computational Methods for Macromolecules}, number = {24}, editor = {Schlick, T. and Gan, H.}, publisher = {Springer}, year = {2002}, language = {en} } @misc{DeuflhardSchuetteCordesetal.1999, author = {Deuflhard, Peter and Sch{\"u}tte, Christof and Cordes, Frank and M{\"u}ller-Kurth, L.}, title = {Konformationsdynamik. Mathematischer Entwurf hochspezifischer Biomolek{\"u}le}, publisher = {In: D. H{\"o}mberg (ed.), 8. Veranstaltungsreihe Forschungspolitische Dialoge in Berlin: Angewandte Mathematik - die verborgene Schl{\"u}sseltechnologie, 30. April 1999, Konrad-Zuse-Zentrum Berlin, pp. 30-34}, year = {1999}, language = {en} } @article{GuerlerMollWeberetal.2007, author = {G{\"u}rler, A. and Moll, Sebastian and Weber, Marcus and Meyer, Holger and Cordes, Frank}, title = {Selection and flexible optimization of binding modes from conformation ensembles}, series = {Biosystems}, journal = {Biosystems}, year = {2007}, language = {en} } @article{GuerlerMollWeberetal.2008, author = {Guerler, A. and Moll, Sebastian and Weber, Marcus and Meyer, Holger and Cordes, Frank}, title = {Selection and flexible optimization of binding modes from conformation ensembles}, series = {Biosystems}, volume = {92}, journal = {Biosystems}, number = {1}, doi = {DOI: 10.1016/j.biosystems.2007.11.004}, pages = {42 -- 48}, year = {2008}, language = {en} } @article{HuisingaBestRoitzschetal.1999, author = {Huisinga, Wilhelm and Best, Christoph and Roitzsch, Rainer and Sch{\"u}tte, Christof and Cordes, Frank}, title = {From Simulation Data to Conformational Ensembles}, series = {J. Comp. Chem.}, volume = {20}, journal = {J. Comp. Chem.}, number = {16}, pages = {1760 -- 1774}, year = {1999}, language = {en} } @article{HuisingaBestCordesetal.1999, author = {Huisinga, Wilhelm and Best, Christoph and Cordes, Frank and Roitzsch, Rainer and Sch{\"u}tte, Christof}, title = {Identification of Molecular Conformations via Statistical Analysis of Simulation Data}, series = {Comp. Chem.}, volume = {20}, journal = {Comp. Chem.}, pages = {1760 -- 1774}, year = {1999}, language = {en} } @article{FoersterBrauerFuersteetal.2007, author = {F{\"o}rster, C. and Brauer, Arnd B. E. and F{\"u}rste, J. and Betzel, C. and Weber, Marcus and Cordes, Frank and Erdmann, V.}, title = {Visualization of the tRNA(Ser) acceptor step binding site in the seryl-tRNA synthetase}, series = {BBRC}, volume = {362}, journal = {BBRC}, number = {2}, pages = {415 -- 418}, year = {2007}, language = {en} } @article{CordesPreissnerSteinke2003, author = {Cordes, Frank and Preissner, Robert and Steinke, Thomas}, title = {How Does a Protein Work?}, series = {BioTOPics J. of Biotechnology Berlin-Brandenburg}, volume = {18}, journal = {BioTOPics J. of Biotechnology Berlin-Brandenburg}, number = {2}, pages = {4 -- 5}, year = {2003}, language = {en} } @inproceedings{NoackWendeSteinkeetal., author = {Noack, Matthias and Wende, Florian and Steinke, Thomas and Cordes, Frank}, title = {A Unified Programming Model for Intra- and Inter-Node Offloading on Xeon Phi Clusters}, series = {SC '14: Proceedings of the International Conference on High Performance Computing, Networking, Storage and Analysis. SC14, November 16-21, 2014, New Orleans, Louisiana, USA}, booktitle = {SC '14: Proceedings of the International Conference on High Performance Computing, Networking, Storage and Analysis. SC14, November 16-21, 2014, New Orleans, Louisiana, USA}, doi = {10.1109/SC.2014.22}, abstract = {Standard offload programming models for the Xeon Phi, e.g. Intel LEO and OpenMP 4.0, are restricted to a single compute node and hence a limited number of coprocessors. Scaling applications across a Xeon Phi cluster/supercomputer thus requires hybrid programming approaches, usually MPI+X. In this work, we present a framework based on heterogeneous active messages (HAM-Offload) that provides the means to offload work to local and remote (co)processors using a unified offload API. Since HAM-Offload provides similar primitives as current local offload frameworks, existing applications can be easily ported to overcome the single-node limitation while keeping the convenient offload programming model. We demonstrate the effectiveness of the framework by using it to enable a real-world application from the field of molecular dynamics to use multiple local and remote Xeon Phis. The evaluation shows good scaling behavior. Compared with LEO, performance is equal for large offloads and significantly better for small offloads.}, language = {en} } @inproceedings{WendeCordesSteinke, author = {Wende, Florian and Cordes, Frank and Steinke, Thomas}, title = {Concurrent Kernel Execution on Xeon Phi within Parallel Heterogeneous Workloads}, series = {Euro-Par 2014: Parallel Processing. 20th International Conference, Porto, Portugal, August 25-29, 2014, Proceedings}, volume = {8632}, booktitle = {Euro-Par 2014: Parallel Processing. 20th International Conference, Porto, Portugal, August 25-29, 2014, Proceedings}, doi = {10.1007/978-3-319-09873-9_66}, pages = {788 -- 799}, language = {en} } @inproceedings{WendeCordesSteinke2012, author = {Wende, Florian and Cordes, Frank and Steinke, Thomas}, title = {On Improving the Performance of Multi-threaded CUDA Applications with Concurrent Kernel Execution by Kernel Reordering}, series = {Application Accelerators in High Performance Computing (SAAHPC), 2012 Symposium on}, booktitle = {Application Accelerators in High Performance Computing (SAAHPC), 2012 Symposium on}, doi = {10.1109/SAAHPC.2012.12}, pages = {74 -- 83}, year = {2012}, language = {en} } @misc{WendeSteinkeCordes, author = {Wende, Florian and Steinke, Thomas and Cordes, Frank}, title = {Multi-threaded Kernel Offloading to GPGPU Using Hyper-Q on Kepler Architecture}, issn = {1438-0064}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-50362}, abstract = {Small-scale computations usually cannot fully utilize the compute capabilities of modern GPGPUs. With the Fermi GPU architecture Nvidia introduced the concurrent kernel execution feature allowing up to 16 GPU kernels to execute simultaneously on a shared GPU device for a better utilization of the respective resources. Insufficient scheduling capabilities in this respect, however, can significantly reduce the theoretical concurrency level. With the Kepler GPU architecture Nvidia addresses this issue by introducing the Hyper-Q feature with 32 hardware managed work queues for concurrent kernel execution. We investigate the Hyper-Q feature within heterogeneous workloads with multiple concurrent host threads or processes offloading computations to the GPU each. By means of a synthetic benchmark kernel and a hybrid parallel CPU-GPU real-world application, we evaluate the performance obtained with Hyper-Q on GPU and compare it against a kernel reordering mechanism introduced by the authors for the Fermi architecture.}, 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}, series = {J. Comp. Chem.}, 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} } @article{HuisingaBestRoitzschetal.1999, author = {Huisinga, Wilhelm and Best, Christoph and Roitzsch, Rainer and Sch{\"u}tte, Christof and Cordes, Frank}, title = {From Simulation Data to Conformational Ensembles}, series = {J. Comp. Chem.}, volume = {20}, journal = {J. Comp. Chem.}, number = {16}, doi = {10.1002/(SICI)1096-987X(199912)20:16<1760::AID-JCC8>3.0.CO;2-2}, pages = {1760 -- 1774}, year = {1999}, language = {en} } @inproceedings{SchuetteCordes2000, author = {Sch{\"u}tte, Christof and Cordes, Frank}, title = {On Dynamical Transitions between Conformational Ensembles}, series = {Molecular Dynamics on Parallel Computers}, booktitle = {Molecular Dynamics on Parallel Computers}, editor = {Esser, R. and Grassberger, P. and Grotendorst, J. and Lewerenz, M.}, publisher = {World Scientific}, doi = {10.1142/9789812793768_0002}, pages = {32 -- 45}, year = {2000}, language = {en} } @article{FischerCordesSchuette1999, author = {Fischer, Alexander and Cordes, Frank and Sch{\"u}tte, Christof}, title = {Hybrid Monte Carlo with adaptive temperature choice}, series = {Comp. Phys. Comm.}, volume = {121}, journal = {Comp. Phys. Comm.}, doi = {10.1016/S0010-4655(99)00274-X}, pages = {37 -- 39}, year = {1999}, 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}, series = {Computational Methods for Macromolecules}, volume = {24}, booktitle = {Computational Methods for Macromolecules}, editor = {Schlick, T. and Gan, H.}, publisher = {Springer}, pages = {235 -- 259}, year = {2002}, language = {en} }