Accuracy evaluation and addition of improved dihedral parameters for the MMFF94s.

The Platinum dataset of protein-bound ligand conformations was used to benchmark the ability of the MMFF94s force field to generate bioactive conformations by minimization of randomly generated conformers. Torsion angle parameters that generally caused wrong geometries were reparameterized by conducting dihedral scans using ab initio calculations at the MP2 level. This reparameterization resulted in a systematic improvement of generated conformations.

DataWarrior: an open-source program for chemistry aware data visualization and analysis.

Drug discovery projects in the pharmaceutical industry accumulate thousands of chemical structures and ten-thousands of data points from a dozen or more biological and pharmacological assays. A sufficient interpretation of the data requires understanding, which molecular families are present, which structural motifs correlate with measured properties, and which tiny structural changes cause large property changes. Data visualization and analysis software with sufficient chemical intelligence to support chemists in this task is rare.

Fighting high molecular weight in bioactive molecules with sub-pharmacophore-based virtual screening.

A new subpharmacophore-based virtual screening method is introduced. Subpharmacophores are derived from large active molecules to detect small bioactive molecules as seeds for starting points in medicinal chemistry programs. A large data set was assembled from the ChEMBL database to check the validity of this approach.

Integration of distributed computing into the drug discovery process.

Grid computing offers an opportunity to gain massive computing power at low costs. We give a short introduction into the drug discovery process and exemplify the use of grid computing for image processing, docking and 3D pharmacophore descriptor calculations. The principle of a grid and its architecture are briefly explained.

OSIRIS, an entirely in-house developed drug discovery informatics system.

We present OSIRIS, an entirely in-house developed drug discovery informatics system. Its components cover all information handling aspects from compound synthesis via biological testing to preclinical development. Its design principles are platform and vendor independence, a consistent look and feel, and complete coverage of the drug discovery process by custom tailored applications.

Comparison of ligand- and structure-based virtual screening on the DUD data set.

Several in-house developed descriptors and our in-house docking tool ActDock were compared with virtual screening on the data set of useful decoys (DUD). The results were compared with the chemical fingerprint descriptor from ChemAxon and with the docking results of the original DUD publication. The DUD is the first published data set providing active molecules, decoys, and references for crystal structures of ligand-target complexes.

Flexophore, a new versatile 3D pharmacophore descriptor that considers molecular flexibility.

A novel pharmacophore descriptor Flexophore is presented, which considers molecular flexibility when comparing descriptor similarities. The descriptor is a complete reduced graph of the underlying molecule. Its nodes are represented by enhanced MM2 atom types, while the edge descriptions encode the molecular flexibility by means of a histogram of node distances in a diverse conformer distribution.