Efficient comprehensive scoring of docked proteincomplexes - a machine learning approach

Biological systems and processes rely on a complex network of molecular interactions. The association of biological macromolecules is a fundamental biochemical phenomenon and an unsolved theoretical problem crucial for the understanding of complex living systems. The term protein-protein docking describes the computational prediction of the assembly of protein complexes from the individual subunits. Docking algorithms generally produce a large number of putative protein complexes. In most cases, some of these conformations resemble the native complex structure within an acceptable degree of structural similarity. A major challenge in the field of docking is to extract the near-native structure(s) out of this considerably large pool of solutions, the so called scoring or ranking problem. It has been the aim of this work to develop methods for the efficient and accurate detection of near-native conformations in the scoring or ranking process of docked protein-protein complexes. A series of structural, chemical, biological and physical properties are used in this work to score docked protein-protein complexes. These properties include specialised energy functions, evolutionary relationship, class specific residue interface propensities, gap volume, buried surface area, empiric pair potentials on residue and atom level as well as measures for the tightness of fit. Efficient comprehensive scoring functions have been developed using probabilistic Support Vector Machines in combination with this array of properties on the largest currently available protein-protein docking benchmark. The established scoring functions are shown to be specific for certain types of protein-protein complexes and are able to detect near-native complex conformations from large sets of decoys with high sensitivity. The specific complex classes are Enzyme-Inhibitor/Substrate complexes, Antibody-Antigen complexes and a third class denoted as "Other" complexes which holds all test cases not belonging to either of the two previous classes. The three complex class specific scoring functions were tested on the docking results of 99 complexes in their unbound form for the above mentioned categories. Defining success as scoring a 'true' result with a p-value of better than 0.1, the scoring schemes were found to be successful in 93%, 78% and 63% of the examined cases, respectively. The ranking of near-native structures can be drastically improved, leading to a significant enrichment of near-native complex conformations in the top ranks. It could be shown that the developed scoring schemes outperform five other previously published scoring functions

Science Plans War Crime: The Humboldt-Universität zu Berlin’s Handling of the National Socialist ‘Generalplan Ost’ (Master Plan for the East)

National Socialist Germany wanted to considerably expand its territory and secure these expansions permanently. In order to organise a gargantuan and complex relocation and settlement campaign in the territories of Eastern Europe conquered as a result of the Second World War, the Reichsführung commissioned scientists from the University of Berlin to develop a so-called ‘Master plan for the East’ (‘Generalplan Ost’). This concept, which was developed in collaboration with scientists, the Reichsleitung (Reich leadership), the SS and the Wehrmacht, precisely describes how the new Lebensraum (living space) was to be made accessible to the German settlers by colonising the territories of the Slavic population and subjecting the people to forced labour, deporting them or murdering them. This book highlights some aspects of the origins and impact of the ‘Generalplan Ost’ and outlines the problematic handling of this war crime at the Humboldt-Universität zu Berlin after the Second World War

Performing within and between analysis (WABA) in Stata

The “fallacies of the wrong level” (e.g., ecological fallacy) are a concern in much of social-science research. When appropriate data are available, researchers frequently use intra-class correlations or ANOVAs to decide whether to use individual-level data or whether to aggregate and analyze data at some higher level, such as workgroups, schools, or locations to examine the associations among theoretical constructs. However, this approach disregards either lower-level information through aggregation or information on group membership by solely using individual-level data. Within and between analysis (WABA), on the other hand, provides a detailed picture of the correlation structure among constructs at different levels by partitioning correlations among constructs into between-groups and within-group components. WABA thus represents a more informative and efficient technique when interested in associations among constructs beyond mere within-group homogeneity. When dealing with more than two hierarchical levels, multiple within and between analysis indicates at which level associations are strongest. Therefore, WABA can also be fruitfully employed to inform model specification in HLM/MLM. In this presentation, I aim to outline the basic ideas and concepts of WABA and to introduce the user-written wabanova program to perform basic single and multiple WABA in Stata.

Dynamic Political Rhetoric: Electoral, Economic, and Partisan Determinants of Speech-Making in the UK Parliament

Parliamentary debate is one major outlet for Members of Parliament (MPs), who spend lots of time preparing for and participating in such discussions. In this paper, we investigate in how far the focus MPs choose in their speeches varies as the economic, partisan and electoral context changes. We choose to study the dynamics nature of speech content in the UK House of Commons, as British MPs enjoy broad discretion regarding the content of their speeches. This paper analyses the constituency, national or partisan focus of all speeches held in the House of Commons between January 1996 and September 2004. We find that government and opposition MPs react differently to contextual changes. Government MPs generally have a higher district focus, which is increased further when the local economy declines and when the governing party becomes more popular

Some remarks on partial orderings of nonnegative definite matrices

AbstractBaksalary and Pukelsheim (1990) investigated partial orderings of nonnegative definite matrices. Some additional remarks are given in this note

Towards obtaining a 3-Decomposition from a perfect Matching

A decomposition of a graph is a set of subgraphs whose edges partition those of $G$. The 3-decomposition conjecture posed by Hoffmann-Ostenhof in 2011 states that every connected cubic graph can be decomposed into a spanning tree, a 2-regular subgraph, and a matching. It has been settled for special classes of graphs, one of the first results being for Hamiltonian graphs. In the past two years several new results have been obtained, adding the classes of plane, claw-free, and 3-connected tree-width 3 graphs to the list. In this paper, we regard a natural extension of Hamiltonian graphs: removing a Hamiltonian cycle from a cubic graph leaves a perfect matching. Conversely, removing a perfect matching $M$ from a cubic graph $G$ leaves a disjoint union of cycles. Contracting these cycles yields a new graph $G_M$. The graph $G$ is star-like if $G_M$ is a star for some perfect matching $M$, making Hamiltonian graphs star-like. We extend the technique used to prove that Hamiltonian graphs satisfy the 3-decomposition conjecture to show that 3-connected star-like graphs satisfy it as well.Comment: 21 pages, 7 figure