title: A combined bioinformatics and chemoinformatics approach for the development of new antiparasitic drugs.
abstract: A modern concept for the development of novel antiparasitic drugs is the combination of bioinformatics and chemoinformatics approaches. This covers, for example, the identification of target proteins serving as molecular points of attack for parasiticides--the idea is that, owing to some essential role, inhibition of a target protein should eradicate the parasite. To prevent toxicity problems for vertebrate host organisms, it is advantageous that these proteins show significant differences from their vertebrate counterparts. In the present work, we identified potential target proteins in parasitic nematodes (Ascaris suum, Brugia malayi, and Haemonchus contortus) and arthropods (Boophilus microplus and Rhipicephalus appendiculatus) using bioinformatic sequence comparison methods on expressed sequence tags. Interesting target proteins (e.g., S-adenosyl-l-methionine synthetase) were characterized in detail by subjecting them to in-depth bioinformatic analysis. S-Adenosyl-l-methionine synthetase was also used to elucidate chemoinformatics approaches like homology modeling and docking, which represent appropriate methods for generating valuable data for the development of new drug candidates.
authors.affiliation: Drug Discovery/BioChemInformatics, Intervet Innovation GmbH, Zur Propstei, 55270 Schwabenheim, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Krasky
authors.forename: A
authors.initials: A
authors.lastname: Rohwer
authors.forename: J
authors.initials: J
authors.lastname: Schroeder
authors.forename: P M
authors.initials: PM
authors.lastname: Selzer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000977:Antiparasitic Agents / Q000737:chemistry*; D001181:Arthropods / Q000187:drug effects / Q000235:genetics; D019295:Computational Biology; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics; D015195:Drug Design; D020224:Expressed Sequence Tags; D015801:Helminth Proteins / Q000187:drug effects / Q000235:genetics; D008716:Methionine Adenosyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009348:Nematoda / Q000187:drug effects / Q000235:genetics; D017386:Sequence Homology, Amino Acid
chemical_list: D000977:Antiparasitic Agents; D015801:Helminth Proteins; D008716:Methionine Adenosyltransferase