TY - GEN A1 - Deuflhard, Peter T1 - From Molecular Dynamics to Conformational Dynamics in Drug Design N2 - Computational drug design studies molecular recognition in the {\em virtual lab}. The arising Hamiltonian dynamics is known to be chaotic and ill-conditioned already after picoseconds, whereas times are $msec$ up to $min$. Classical molecular dynamics with long term trajectory computation gives, at best, information about time and statistical ensemble averages. The present paper surveys a recent new modeling approach called {\em conformational dynamics}, which is due to the author and Ch. Schütte. This approach achieves information about the dy time scales by telescoping a short term deterministic model with a statistical model. Examples of small biomolecules are included. T3 - ZIB-Report - 02-20 KW - molecular dynamics KW - conformational dynamics KW - drug design KW - Hamiltonian dynamics KW - almost invariant sets KW - transition operator KW - Markov chain KW - Perro Y1 - 2002 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-6878 ER - TY - GEN A1 - Weber, Marcus A1 - Rungsarityotin, Wasinee A1 - Schliep, Alexander T1 - Perron Cluster Analysis and Its Connection to Graph Partitioning for Noisy Data N2 - The problem of clustering data can be formulated as a graph partitioning problem. Spectral methods for obtaining optimal solutions have reveceived a lot of attention recently. We describe Perron Cluster Cluster Analysis (PCCA) and, for the first time, establish a connection to spectral graph partitioning. We show that in our approach a clustering can be efficiently computed using a simple linear map of the eigenvector data. To deal with the prevalent problem of noisy and possibly overlapping data we introduce the min Chi indicator which helps in selecting the number of clusters and confirming the existence of a partition of the data. This gives a non-probabilistic alternative to statistical mixture-models. We close with showing favorable results on the analysis of gene expressi on data for two different cancer types. T3 - ZIB-Report - 04-39 KW - Perron cluster analysis KW - spectral graph theory KW - clustering KW - gene expression Y1 - 2004 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-8140 ER - TY - GEN A1 - Deuflhard, Peter A1 - Weber, Marcus T1 - Robust Perron Cluster Analysis in Conformation Dynamics N2 - 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. T3 - ZIB-Report - 03-19 KW - Markov chains KW - cluster algorithms KW - Perron cluster analysis KW - conformation dynamics Y1 - 2003 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-7415 ER - TY - GEN A1 - Weber, Marcus T1 - Clustering by using a simplex structure N2 - In this paper we interpret clustering as a mapping of data into a simplex. If the data itself has simplicial struture this mapping becomes linear. Spectral analysis is an often used tool for clustering data. We will show that corresponding singular vectors or eigenvectors comprise simplicial structure. Therefore they lead to a cluster algorithm, which consists of a simple linear mapping. An example for this kind of algorithms is the Perron cluster analysis (PCCA). We have applied it in practice to identify metastable sets of molecular dynamical systems. In contrast to other algorithms, this kind of approach provides an a priori criterion to determine the number of clusters. In this paper we extend the ideas to more general problems like clustering of bipartite graphs. T3 - ZIB-Report - 04-03 KW - cluster algorithms KW - Perron cluster analysis KW - stochastic matrices KW - bipartite graphs Y1 - 2003 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-7782 ER - TY - GEN A1 - Kube, Susanna A1 - Weber, Marcus T1 - Coarse Grained Molecular Kinetics N2 - The dynamic behavior of molecules can often be described by Markov processes. From computational molecular simulations one can derive transition rates or transition probabilities between subsets of the discretized conformational space. On the basis of this dynamic information, the spatial subsets are combined into a small number of so-called metastable molecular conformations. This is done by clustering methods like the Robust Perron Cluster Analysis (PCCA+). Up to now it is an open question how this coarse graining in space can be transformed to a coarse graining of the Markov chain while preserving the essential dynamic information. In the following article we aim at a consistent coarse graining of transition probabilities or rates on the basis of metastable conformations such that important physical and mathematical relations are preserved. This approach is new because PCCA+ computes molecular conformations as linear combinations of the dominant eigenvectors of the transition matrix which does not hold for other clustering methods. T3 - ZIB-Report - 06-35 Y1 - 2006 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-9299 ER - TY - GEN A1 - Weber, Marcus A1 - Walter, Lionel A1 - Kube, Susanna A1 - Deuflhard, Peter T1 - Stable computation of probability densities for metastable dynamical systems N2 - Whenever the invariant stationary density of metastable dynamical systems decomposes into almost invariant partial densities, its computation as eigenvector of some transition probability matrix is an ill-conditioned problem. In order to avoid this computational difficulty, we suggest to apply an aggregation/disaggregation method which only addresses wellconditioned sub-problems and thus results in a stable algorithm. In contrast to existing methods, the aggregation step is done via a sampling algorithm which covers only small patches of the sampling space. Finally, the theoretical analysis is illustrated by two biomolecular examples. T3 - ZIB-Report - 06-39 KW - dynamical systems KW - metastability KW - molecular conformations KW - cluster analysis KW - sampling KW - aggregation/disaggregation KW - domain decomposition Y1 - 2006 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-9331 ER - TY - GEN A1 - Kube, Susanna A1 - Weber, Marcus T1 - Identification of Metastabilities in Monomolecular Conformation Kinetics N2 - The identification of metastable conformations of molecules plays an important role in computational drug design. One main difficulty is the fact that the underlying dynamic processes take place in high dimensional spaces. Although the restriction of degrees of freedom to a few dihedral angles significantly reduces the complexity of the problem, the existing algorithms are time-consuming. They are based on the approximation of transition probabilities by an extensive sampling of states according to the Boltzmann distribution. We present a method which can identify metastable conformations without sampling the complete distribution. Our algorithm is based on local transition rates and uses only pointwise information about the potential energy surface. In order to apply the cluster algorithm PCCA+, we compute a few eigenvectors of the rate matrix by the Jacobi-Davidson method. Interpolation techniques are applied to approximate the thermodynamical weights of the clusters. The concluding example illustrates our approach for epigallocatechine, a molecule which can be described by seven dihedral angles. T3 - ZIB-Report - 06-01 KW - metastable conformations KW - potential energy surface KW - transition rates KW - eigenvectors KW - clustering Y1 - 2005 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-8956 ER - TY - GEN A1 - Deuflhard, Peter T1 - Differential Equations in Technology and Medicine. Computational Concepts, Adaptive Algorithms, and Virtual Labs N2 - This series of lectures has been given to a class of mathematics postdocs at a European summer school on Computational Mathematics Driven by Industrial Applications in Martina Franca, Italy (organized by CIME). It deals with a variety of challenging real life problems selected from clinical cancer therapy, communication technology, polymer production, and pharmaceutical drug design. All of these problems from rather diverse application areas share two common features: (a) they have been modelled by various differential equations -- elliptic, parabolic, or Schrödinger--type partial differential equations, countable ordinary diffential equations, or Hamiltonian systems, (b) their numerical solution has turned out to be real challenge to computational mathematics. T3 - ZIB-Report - SC-99-34 KW - differential equations: KW - ordinary KW - partial KW - countable KW - hamiltonian KW - finite element methods: KW - adaptive KW - multilevel KW - grid generation KW - medical t Y1 - 1999 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-4223 ER - TY - GEN A1 - Helmberg, Christoph A1 - Kiwiel, K.C. T1 - A Spectral Bundle Method with Bounds N2 - Semidefinite relaxations of quadratic 0-1 programming or graph partitioning problems are well known to be of high quality. However, solving them by primal-dual interior point methods can take much time even for problems of moderate size. The recent spectral bundle method of Helmberg and Rendl can solve quite efficiently large structured equality-constrained semidefinite programs if the trace of the primal matrix variable is fixed, as happens in many applications. We extend the method so that it can handle inequality constraints without seriously increasing computation time. Encouraging preliminary computational results are reported. T3 - ZIB-Report - SC-99-37 KW - Eigenvalue optimization KW - convex optimization Y1 - 1999 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-4256 ER - TY - GEN A1 - Zha, Hongyuan T1 - A Numerical Algorithm for Computing the Restricted Singular Value Decomposition of Matrix Triplets. N2 - This paper presents a numerical algorithm for computing the restricted singular value decomposition of matrix triplets (RSVD). It is shown that one can use unitary transformations to separate the regular part from a general matrix triplet. After preprocessing on the regular part, one obtains a matrix triplet consisting of three upper triangular matrices of the same dimensions. The RSVD of this special matrix triplet is computed using the implicit Kogbetliantz technique. The algorithm is well suited for parallel computation. {\bf Keywords:} Restricted singular values, matrix triplets, unitary transformations, implicit Kogbetliantz technique. T3 - ZIB-Report - SC-89-01 KW - restricted singular values KW - matrix triplets KW - unitary transformations KW - implicit Kogbetliantz technique Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-194 ER - TY - GEN A1 - Weber, Marcus T1 - Eigenvalues of non-reversible Markov chains – A case study N2 - Finite reversible Markov chains are characterized by a transition matrix P that has real eigenvalues and pi-orthogonal eigenvectors, where pi is the stationary distribution of P. This means, that a transition matrix with complex eigenvalues corresponds to a non-reversible Markov chain. This observation leads to the question, whether the imaginary part of that eigendecomposition corresponds to or indicates the “pattern” of the nonreversibility. This article shows that the direct relation between imaginary parts of eigendecompositions and the non-reversibility of a transition matrix is not given. It is proposed to apply the Schur decomposition of P instead of the eigendecomposition in order to characterize its nonreversibility. T3 - ZIB-Report - 17-13 KW - non-reversible KW - transition matrix KW - detailed balance Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-62191 SN - 1438-0064 ER -