pharmACOphore: multiple flexible ligand alignment based on ant colony optimization

info:eu-repo/semantics/publishe

A resting state network in the motor control circuit of the basal ganglia

<p>Abstract</p> <p>Background</p> <p>In the absence of overt stimuli, the brain shows correlated fluctuations in functionally related brain regions. Approximately ten largely independent resting state networks (RSNs) showing this behaviour have been documented to date. Recent studies have reported the existence of an RSN in the basal ganglia - albeit inconsistently and without the means to interpret its function. Using two large study groups with different resting state conditions and MR protocols, the reproducibility of the network across subjects, behavioural conditions and acquisition parameters is assessed. Independent Component Analysis (ICA), combined with novel analyses of temporal features, is applied to establish the basis of signal fluctuations in the network and its relation to other RSNs. Reference to prior probabilistic diffusion tractography work is used to identify the basal ganglia circuit to which these fluctuations correspond.</p> <p>Results</p> <p>An RSN is identified in the basal ganglia and thalamus, comprising the pallidum, putamen, subthalamic nucleus and substantia nigra, with a projection also to the supplementary motor area. Participating nuclei and thalamo-cortical connection probabilities allow this network to be identified as the motor control circuit of the basal ganglia. The network was reproducibly identified across subjects, behavioural conditions (fixation, eyes closed), field strength and echo-planar imaging parameters. It shows a frequency peak at 0.025 ± 0.007 Hz and is most similar in spectral composition to the Default Mode (DM), a network of regions that is more active at rest than during task processing. Frequency features allow the network to be classified as an RSN rather than a physiological artefact. Fluctuations in this RSN are correlated with those in the task-positive fronto-parietal network and anticorrelated with those in the DM, whose hemodynamic response it anticipates.</p> <p>Conclusion</p> <p>Although the basal ganglia RSN has not been reported in most ICA-based studies using a similar methodology, we demonstrate that it is reproducible across subjects, common resting state conditions and imaging parameters, and show that it corresponds with the motor control circuit. This characterisation of the basal ganglia network opens a potential means to investigate the motor-related neuropathologies in which the basal ganglia are involved.</p

Kontroverse Positionen im Inklusionsdiskurs

Exner K, te Poel K. Kontroverse Positionen im Inklusionsdiskurs. Presented at the Prä-Konferenz der Bielefelder Frühjahrstagung

Chemistry Central Journal Poster presentation The influence of protonation in protein-ligand docking

© 2008 Brink and Exner With the use in Virtual Screening (VS) in experiments Protein-Ligand-Docking has gained more and more importance in pharmaceutical research over the past years. To model the interactions between the protein and a ligand empirical scoring functions are used in many programs. These scoring functions consist of different terms, which describe physical and chemical properties important for an attractive interaction between the protein and the ligand. Most scoring functions use hydrogen bonds and salt bridges as descriptors. For both the knowledge of the protein&apos;s and the ligand&apos;s protonation state is important but experimental methods like x-ray crystallography do not resolve the hydrogen atom positions in protein structures

Open Access

molecules and multiple ligand

Chemistry Central Journal Poster presentation New and improved features of the docking software PLANTS

© 2009 Exner et al; licensee BioMed Central Ltd. We will summarize the latest developments for our protein-ligand docking software PLANTS (Protein-Ligand ANT System) [1][2][3]. This will include the pre-processing of the ligands and the protein performed by the program SPORES (Structure PrOtonation and REcognition System), parameterization of a new scoring function, as well as the inclusion of additional degrees of freedom into the docking process like flexible side chains and essential water molecules. The use of constraints from experimental data for improving the docking poses will be presented. Finally, an outlook towards the possible usage of the PLANTS approach for the flexible alignment of multipl