Biomedical subjects

Thierry Langer

Publications and source records attributed to Thierry Langer.

39 records · Page 3Linked to original sources

PubMedDate not supplied

Influence of the conditions in pharmacophore generation, scoring, and 3D database search for chemical feature-based pharmacophore models: one application study of ETA- and ETB-selective antagonists.

Using the commercial pharmacophore modeling suite Catalyst, we have studied the influence of the compare.scaledMultiBlobFeatureErrors . Catalyst parameter. The influence of this parameter has been studied in pharmacophore generation, hypothesis scoring, and database searching. This parameter, introduced in Catalyst 4.7, changed its default value in Catalyst 4.8, and it strongly influences the statistical quality of pharmacophore generation, scoring of the hypotheses, and database searching. Two different pharmacophore models have been constructed for the ETA and ETB receptor antagonists. Both models contain one positive ionizable, one negative ionizable, one hydrogen-bond acceptor, one hydrophobic aromatic, and one hydrophobic aliphatic feature. The models have been compared, and some differences in the position of the hydrogen-bond acceptor in the putative binding pocket have been highlighted.

Database Management Systems↗

PubMedDate not supplied

Comparative performance assessment of the conformational model generators omega and catalyst: a large-scale survey on the retrieval of protein-bound ligand conformations.

In continuation of our studies to evaluate the ability of various conformer generators to produce bioactive conformations, we present the extension of our work on the analysis of Catalyst's conformational subsampling algorithm in a comparative evaluation with OpenEye's currently updated tool Omega 2.0. Our study is based on an enhanced test set of 778 drug molecules and pharmacologically relevant compounds extracted from the Protein Data Bank (PDB). We elaborated protocols for two common conformer generation use cases and applied them to both programs: (i) high-throughput settings for processing large databases and (ii) high-quality settings for binding site exploration or lead structure refinement. While Catalyst is faster in the first case, Omega 2.0 better reproduces the bound ligand conformations from the PDB in less time for the latter case.

Catalysis↗

PubMedDate not supplied

Parallel screening: a novel concept in pharmacophore modeling and virtual screening.

Parallel screening comprises a novel in silico method to predict the potential biological activities of a compound by screening it with a multitude of pharmacophore models. Our aim is to provide a fast, large-scale system that allows for virtual activity profiling. In this proof of principle study, carried out with the software tools LigandScout and Catalyst, we present a model work for the application of parallel pharmacophore-based virtual screening on a set of 50 structure-based pharmacophore models built for various viral targets and 100 antiviral compounds. The latter were screened against all pharmacophore models in order to determine if their biological targets could be correctly predicted via an enrichment of corresponding pharmacophores matching these ligands. The results demonstrate that the desired enrichment, that is, successful virtual activity profiling, was achieved for approximately 90% of all input molecules. We discuss descriptors for output validation, as well as various aspects influencing the analysis of the obtained activity profiles, and the effect of the utilized search modus for screening.

Antiviral Agents↗