Wolfgang Heiden

A new approach to analysis and display of local lipophilicity/hydrophilicity mapped on molecular surfaces.

SummaryA new method for display and analysis of lipophilic/hydrophilic properties on molecular surfaces is presented. The present approach is based on the concept of Crippen and coworkers that the overall hydrophobicity of a molecule (measured as the logarithm of the partition coefficient in an octanol/water system) can be obtained as a superposition of single atom contributions. It is also based on the concept of molecular lipophilicity potentials (MLP) first introduced by Audry and coworkers in order to establish a 3D lipophilicity potential profile in the molecular environment. Instead of using a l/r- or an exponential distance law between the atomic coordinates and a point on the molecular surface, a new distance dependency is introduced for the calculation of an MLP-value on the solvent-accessible surface of the molecule. In the present formalism the Crippen values (introduced for atoms in their characteristic structural environment) are ‘projected’ onto the van der Waals surface of the molecule by a special weighting procedure. This guarantees that only those atomic fragments contribute significantly to the surface values that are in the close neighbourhood of the surface point. This procedure not only works for small molecules but also allows the characterization of the surfaces of biological macromolecules by means of local lipophilicity. Lipophilic and hydrophilic domains can be recognized by visual inspection of computer-generated images or by computational procedures using fuzzy logic strategies. Local hydrophobicities on different molecular surfaces can be quantitatively compared on the basis of the present approach.

Fast generation of molecular surfaces from 3D data fields with an enhanced “marching cube” algorithm

An improved version of the “marching cubes” algorithm [W. Lorensen and H. Cline, Comp. Graph. 21, (1987)] for the generation of isosurfaces from 3D data fields is presented and applied to molecular surfaces. The new algorithm avoids inconsistent pattern definitions of the original one, which lead to artificial gaps. The advantage of a logarithmic interpolation procedure, in particular for data fields typically occurring in molecular science, is demonstrated. An example is the generation of molecular surfaces based upon electron density data.

MOLCAD — Computer Aided Visualization and Manipulation of Models in Molecular Science

Visualization techniques in the field of molecular science as realized in the modeling package MOLCAD are described. The MOLCAD package was developed in the group of the authors. It provides state of the art interactive techniques for display and manipulation of three dimensional molecular structures, and molecular properties. MOLCAD offers the standard features used in the field of molecular modeling and advanced tools for the visualization of related data. The visualization techniques are described, and some examples for the application are given.

Triangulation algorithms for the representation of molecular surface properties

SummaryA triangulation algorithm for a dotted surface (i.e. a surface defined by point coordinates in three dimensions) is given. The individual triangles are generated on the basis of a hierarchy of strategies according to increasing surface complexity. While for small molecules an elementary algorithm is sufficient to triangulate the surface, large molecules-like proteins-generally need all steps of the hierarchy. Although this program has been developed with the aim of triangulating molecular surfaces, it can in principle be applied to any surface defined by 3D point coordinates.

Segmentation of protein surfaces using fuzzy logic.

An algorithm has been developed that can be used to divide triangulated molecular surfaces into distinct domains on the basis of physical and topographical molecular properties. Domains are defined by a certain degree of homogeneity concerning one of these properties. The method is based on fuzzy logic strategies, thus taking into consideration the smooth changes of the properties considered along complex macromolecular surfaces. Scalar qualities assigned to every node point on a triangulated surface are translated into linguistic variables, which can then be processed using a special fuzzy dissimilarity operator. Possible applications are demonstrated using surface segmentation for properties like electrostatic potential, lipophilicity and shape for the analysis of serine proteinase substrate/inhibitor specificity.

Empirical Method for the Quantification and Localization of Molecular Hydrophobicity

An empirical method for the localization, the quantification, and the analysis of relative hydrophobicity of a molecule or a molecular fragment is presented. The approach is based on two concepts: (i) that the overall hydrophobicity of a molecule (measured, for example, by the logarithm of the partition coefficient in an octanoYwater system log(P) = AG,,,fed-2.303RT with the transfer free energy AGuansfer for one mole substance from one solvent to the other) can be obtained as a superposition of fragmental contributions and (ii) that this free energy can be represented as a surface integral over the solvent accessible surface of the molecule on the basis of a local surface density e. This surface density function is represented in terms of a three-dimensional scalar field which is composed as a sum of atomic increment functions describing lipophilicity in the molecular environment. For these atomic increment functions a nonlinear distance law is postulated between the atomic coordinates and any point in space. This law guarantees that only those atomic fragments contribute significantly to the surface values, which are in close neighborhood of the surface point. Free parameters for the distance function and for characteristic increment contribution to the surface density are determined on the basis of experimental log P values for the 1-octanoYwater system. It is demonstrated with a few examples that the procedure not only works for the prediction of unknown partition coefficients but also for the localization and quantification of the contribution of arbitrary fragments to this quantity. The formalism can be used also for an estimation of the hydrophobicity index, a hypothetical log P value which depends on the actual molecular conformation.

The influence of tetraphenylborates (hydrophobic anions) on yeast cell electro-rotation

The action of a series of tetraphenylborate ion (TPB) derivatives on yeast cells was studied by electro-rotation of the pre-treated cells. TPB derivatives in which all four phenyl groups were substituted with fluorine, chlorine or trifluoromethyl were much more toxic than the unsubstituted compound, the effect increasing dramatically with increasing size of substituents. These observations suggest that the toxicity of these hydrophobic ions is determined mainly by their size and possibly also by the chemical inductivity of their substituent groups. The order of the toxicities of these ions was in fair agreement with literature values for their translocation rates across artificial bilayers. Incubation times of 3 h were used as standard, longer incubations (up to 48 h) showed that the number of cells affected by low doses of TPB increased with the logarithm of time after the first hour of incubation. Although measurements of the percentage of cells showing co-field rotation showed that controls were not adversely affected by incubations as long as 9 h, rotation spectra showed that some cells suffer loss of internal conductivity during extended incubations. Decrease of the pH of the incubation medium, or inclusion of high concentrations of NaCl or KCl, potentiated the effects of these hydrophobic ions. The toxicity developed slowly, and the sensitivity of the assay was only very weakly dependent on the cell suspension density.

Marching Cube-Algorithmen zur schnellen Generierung von Isoflachen auf der Basis dreidimensionaler Datenfelder

Die Visualisierung und Quantifizierung von Datenfeldern im dreidimensionalen Raum gewinnt in vielen Bereichen von Wissenschaft und Technik mehr und mehr an Bedeutung. Anschauliche Visualisierung der Daten stellt eine Voraussetzung fur effektive Kommunikation zwischen Mensch und Maschine dar. Dies last sich mit Hilfe der Computergraphik durch die Darstellung von Isoflachen, die einen bestimmten Datenwert reprasentieren, erreichen. Fur die Visualisierung zeitabhangiger Resultate (z.B. dynamische Simulationen) sowie zur hochgradig interaktiven Bearbeitung der Daten sind extrem schnelle Computerprogramme zur Generierung dieser Isooberflachen erforderlich. Ein Beispiel fur einen derartigen Algorithmus ist die hier vorgestellte Triangulation dreidimensionaler Gitter auf der Basis einzelner Wurfel als Gitterelemente.

FIVIS bicycle simulator: an immersive game platform for physical activities

The objective of the FIVIS project is to develop a bicycle simulator which is able to simulate real life bicycle ride situations as a virtual scenario within an immersive environment. A sample test bicycle is mounted on a motion platform to enable a close to reality simulation of turns and balance situations. The visual field of the bike rider is enveloped within a multi-screen visualization environment which provides visual data relative to the motion and activity of the test bicycle. This implies the bike rider has to pedal and steer the bicycle as they would a traditional bicycle, while forward motion is recorded and processed to control the visualization. Furthermore, the platform is fed with real forces and accelerations that have been logged by a mobile data acquisition system during real bicycle test drives. Thus, using a feedback system makes the movements of the platform reflect the virtual environment and the reaction of the driver (e.g. steering angle, step rate).

Atmosphaeres – 360° Video Environments for Stress and Pain Management

The Atmosphaeres project aims to reduce sufferers’ stress and pain levels by using 360° video environments that are presented in a highly immersive Head-Mounted Display (HMD). Here we report first insights of our prototype combination of the 360° video environments and the Oculus Rift, the HMD used for our project. We find that our ‘Atmosphaeres’ are capable of truly transporting the user to another, virtually created location, however, there were a number of restrictions with the first system, including image quality and nausea which we hope to eliminate with the system we present in this paper. There are also a number of research questions that need to be considered for the use of the Atmosphaeres in stress and pain management or for general relaxation purposes. These questions include whether 360° video environments are capable of reducing stress and experienced pain and whether changes to the Oculus Rift DK2 do in fact reduce the nausea that was often caused by the DK1. Sound is another important yet often under-considered factor in many Virtual Reality applications and questions we seek to answer revolve around how the quality and type of audio contribute to users’ feeling of presence and ultimately their stress and pain levels.