Ligand-based Improvement of an Atomistic Protein Model (BgAChBP) by Bioinformatical Methods

Nicotinic acetylcholine receptors (AChR) are of central physiological and clinical relevance. This research field has been greatly stimulated by the discovery of the acetylcholine-binding proteins (AChBP) in some gastropods. They correspond to the ligand-binding domain of nAChR, but in contrast to these membrane-bound receptors, they are water soluble proteins. Therefore, their analysis is much easier. There exist many other ligands besides acetylcholine, including well known toxins such as nicotine, cobratoxin and strychnine. From a freshwater snail, the Markl group recently purified a novel AChBP (termed BgAChBP), encompassing 60 subunits instead of only five as usual. Its very special structure (a pentagonal dodecahedron) has been analyzed, and it has been recombinantly expressed. Now the focus is on the ligand binding properties and the exact structure of the ligand binding sites. Computer-aided prediction of molecular complex structures, notably the “docking” of ligands to proteins, is a major topic of the Hildebrandt group. Docking procedures are primarily applied in the search of new drug molecules. In the present cooperation, they will be used to improve and validate 3D structure models of the new AChBP.