Algorithm engineering for optimal alignment of protein structure distance matrices

Protein structural alignment is an important problem in computational biology. In this paper, we present first successes on provably optimal pairwise alignment of protein inter-residue distance matrices, using the popular Dali scoring function. We introduce the structural alignment problem formally, which enables us to express a variety of scoring functions used in previous work as special cases in a unified framework. Further, we propose the first mathematical model for computing optimal structural alignments based on dense inter-residue distance matrices. We therefore reformulate the problem as a special graph problem and give a tight integer linear programming model. We then present algorithm engineering techniques to handle the huge integer linear programs of real-life distance matrix alignment problems. Applying these techniques, we can compute provably optimal Dali alignments for the very first time

Genetic alterations of the SUMO isopeptidase SENP6 drive lymphomagenesis and genetic instability in diffuse large B-cell lymphoma

SUMOylation is a post-translational modification of proteins that regulates these proteins' localization, turnover or function. Aberrant SUMOylation is frequently found in cancers but its origin remains elusive. Using a genome-wide transposon mutagenesis screen in a MYC-driven B-cell lymphoma model, we here identify the SUMO isopeptidase (or deconjugase) SENP6 as a tumor suppressor that links unrestricted SUMOylation to tumor development and progression. Notably, SENP6 is recurrently deleted in human lymphomas and SENP6 deficiency results in unrestricted SUMOylation. Mechanistically, SENP6 loss triggers release of DNA repair- and genome maintenance-associated protein complexes from chromatin thereby impairing DNA repair in response to DNA damages and ultimately promoting genomic instability. In line with this hypothesis, SENP6 deficiency drives synthetic lethality to Poly-ADP-Ribose-Polymerase (PARP) inhibition. Together, our results link SENP6 loss to defective genome maintenance and reveal the potential therapeutic application of PARP inhibitors in B-cell lymphoma

An algorithm for the protein docking problem

We have implemented a parallel distributed geometric docking algorithm that uses a new measure for the size of the contact area of two molecules. The measure is a potential function that counts the 'van der Waals contacts' between the atoms of the two molecules (the algorithm does not compute the Lennard-Jones potential). An integer constant c_a is added to the potential for each pair of atoms whose distance is in a certain interval. For each pair whose distance is smaller than the lower bound of the interval an integer constant c_s is subtracted from the potential (c_a < c_s). The number of allowed overlapping atom pairs is handled by a third parameter N. Conformations where more than N atom pairs overlap are ignored. In our 'real world' experiments we have used a small parameter N that allows small local penetration. Among the best five dockings found by the algorithm there was almost always a good (rms) approximation of the real conformation. In 42 of 52 test examples the best conformation with respect to the potential function was an approximation of the real conformation. The running time of our sequential algorithm is in the order of the running time of the algorithm of Norel et al. [NLW+]. The parallel version of the algorithm has a reasonable speedup and modest communication requirements. (orig.)Available from TIB Hannover: RR 1912(95-1-023) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Dilation-optimal edge deletion in polygonal cycles

Consider a geometric network G in the plane. The dilation between any two vertices x and y in G is the ratio of the shortest path distance between x and y in G to the Euclidean distance between them. The maximum dilation over all pair of vertices in G is called the dilation of G. In this paper, a randomized algorithm is presented which, when given a polygonal cycle C on n vertices in the plane, computes in O(n log 3 n) expected time, the edge of C whose removal results in a polygonal path of smallest possible dilation. It is also shown that the edge whose removal gives a polygonal path of largest possible dilation can be computed in O(n log n) time. If C is a convex polygon, the running time for the latter problem becomes O(n). Finally, it is shown that a (1 − ǫ)-approximation to the dilation of all the path C \ {e}, for all edge e of C, can be computed in O(n log n) total time.

Translating a planar object to maximize point containment

Abstract. Let C be a compact set in

Archeologische Rapporten bergen op Zoom 2

Een kleinschalig onderzoek in de binnenstad, op een achtererf van de Goudenbloemstraat. Bij het uitgraven van een grote vijver stuitte de eigenaar op skeletresten. Nader onderzoek wees uit dat onder de tuin de oude grens tussen het Minderbroederkerkhof en het huisperceel gesitueerd was. Twee begravingen in situ dateerden uit de 16de of 17de eeuw. Oudere sporen bestonden uit een greppel uit de 14de eeuw en een omvangrijke beerkuil uit de vroege 16de eeuw