The Helmholtz Network for Bioinformatics: an integrative web portal for bioinformatics resources.

SUMMARY: The Helmholtz Network for Bioinformatics (HNB) is a joint venture of eleven German bioinformatics research groups that offers convenient access to numerous bioinformatics resources through a single web portal. The 'Guided Solution Finder' which is available through the HNB portal helps users to locate the appropriate resources to answer their queries by employing a detailed, tree-like questionnaire. Furthermore, automated complex tool cascades ('tasks'), involving resources located on different servers, have been implemented, allowing users to perform comprehensive data analyses without the requirement of further manual intervention for data transfer and re-formatting. Currently, automated cascades for the analysis of regulatory DNA segments as well as for the prediction of protein functional properties are provided. AVAILABILITY: The HNB portal is available at http://www.hnbioinfo.de

FlexE: efficient molecular docking considering protein structure variations.

Side-chain or even backbone adjustments upon docking of different ligands to the same protein structure, a phenomenon known as induced fit, are frequently observed. Sometimes point mutations within the active site influence the ligand binding of proteins. Furthermore, for homology derived protein structures there are often ambiguities in side-chain placement and uncertainties in loop modeling which may be critical for docking applications. Nevertheless, only very few molecular docking approaches have taken into account such variations in protein structures. We present the new software tool FlexE which addresses the problem of protein structure variations during docking calculations. FlexE can dock flexible ligands into an ensemble of protein structures which represents the flexibility, point mutations, or alternative models of a protein. The FlexE approach is based on a united protein description generated from the superimposed structures of the ensemble. For varying parts of the protein, discrete alternative conformations are explicitly taken into account, which can be combinatorially joined to create new valid protein structures.FlexE was evaluated using ten protein structure ensembles containing 105 crystal structures from the PDB and one modeled structure with 60 ligands in total. For 50 ligands (83 %) FlexE finds a placement with an RMSD to the crystal structure below 2.0 A. In all cases our results are of similar quality to the best solution obtained by sequentially docking the ligands into all protein structures (cross docking). In most cases the computing time is significantly lower than the accumulated run times for the single structures. FlexE takes about five and a half minutes on average for placing one ligand into the united protein description on a common workstation. The example of the aldose reductase demonstrates the necessity of considering protein structure variations for docking calculations. We docked three potent inhibitors into four protein structures with substantial conformational changes within the active site. Using only one rigid protein structure for screening would have missed potential inhibitors whereas all inhibitors can be docked taking all protein structures into account.

Evidence of inherent spontaneous polarization in the metazoan integument epithelia.

The live integument epithelia of the metazoa have an inherent spontaneous polarization (an inherent permanent electric dipole moment) of corresponding direction perpendicular to the integument surface. The existence of the inherent polarization was proved by their temperature dependence, i.e., by the pyroelectric (PE) effect. Quantitative PE measurements were carried out on a number of integument epithelia of vertebrates (a) in vivo, (b) on fresh epidermis preparations, and (c) on dead, air-dried epidermis specimens of the same species. The demonstrated spontaneous polarization is not dependent on the living state and not caused by a potential difference between the outer and inner integument surface. Dead, dry epidermis samples (potential difference less than 0.01 mV) as well as dead, dry integument appendages (bristles, hairs), and dead cuticles (of arthropoda, annelida, nematoda) showed an inherent dipole moment of the same orientation as the live epidermis. The findings reveal a relationship between the direction (vector) of inherent spontaneous polarization and that of growth (morphogenesis) in the animal epidermis, their appendages, and cuticles. We conclude (a) that the inherent spontaneous polarization is present in live individual epithelial cells of the metazoan integument, and (b) that this physical property is related to the structural and functional cell polarity of integument epithelia and possibly of other epithelia.

Epidermis of human skin: pyroelectric and piezoelectric sensor layer.

The epidermis of live human skin has a permanent electric dipole moment perpendicular to its surface. Voltage responses to a rapid change of temperature are pyroeletric, while voltage responses to pressure pulses are piezoelectric in nature. The time course of the responses depends on dX/dt (X, temperature or pressure). The epidermal surface can react to all physical environmental influences to which nonbiological pyroelectric materials are known to respond. Epidermal voltage signals can be perceived through the intraepidermal and the superficial dermal nervous network. The pyroelectric and piezoelectric properties are also measurable on dead, dry skin samples.

Evidence for pyroelectric and piezoelectric sensory mechanisms in the insect integument.

Quantitative pyroelectric (PE) and piezoelectric (PZE) measurements were carried out on the insect integument of live Blaberus giganteus (cockroach) and on dry integument preparations of the same species. Voltage responses to optical pulses of 10--500 ms, absorbed in the live integument, were PE: interference filter measurements showed the responses to be proportional to the absorbed thermal radiation flux and independent of the wavelength. The voltage/time-course of the responses was in agreement with theoretically calculated PE signals. Voltage responses to mechanical pulses were PZE. The responses of the inner and outer integument surfaces always had opposite electric signs. The polar character of the integument was confirmed by means of a separate dielectric heating method. To explain these results, we hypothesize that the PE properties are for the most part localized in the two outermost layers (outer and inner epicuticle) of the integument, which consists mainly of polar lipids and proteins. Parallel alignment of these polar molecules perpendicular to the integument surface is very likely. PE and PZE responses, therefore, will not only occur in live insects but will also be measurable in dead, dry integument preparations as long as the polar tissue texture remains intact. Due to its polar texture, the insect integument will react to rapid changes in temperature, illumination, or uniaxial pressure in the same way as nonbiological PE materials, where the voltage responses depend on dX/dt (X, pressure or temperature). It seems clear, therefore, that the well-known physiological reactions of various arthropods to such physical outside influences may be related to the PE property of their integument.