Mos. Gund Techniques to Search Confor ational Space for Cholinergic Ligands

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The acetylcholine receptor is a representative of a large class of membrane proteins responsible for the electrical activity of the nervous system. The receptor is involved in many biologically important processes, such as regulation of sleep, memory and learning processes. Understanding the structure and function of the receptor as well as being able to predict active ligands will greatly further our understanding of these important biological molecules. Dr. Gund proposes to develop a computational method to systematically survey molecular conformations for large molecules with many degrees of conformational freedom for the CYBER 205 vector supercomputer. She will then relay information from the conformational calculations as well as from molecular dynamics calculations on the CYBER in real time to a VAX based molecular modeling system for further interactive manipulations. Other objectives will involve relaying information from ab initio and molecular mechanics calculations to a VAX based molecular modeling system. The applications of these objectives will be to determine the bioactive conformations of cholinergic ligands including polypeptides, receptor mapping, calculation of conformational states of receptor-ligand bound and unbound complexes, and design of new ligands which would explore the topography and mechanism of receptor-ligand binding.