Molecular Modeling in Drug Design for the Development of Organophosphorous Antidotes/Prophylactics
Abstract
A Molecular modeling facility had been setup for modeling of muscarinic agonists, antagonists and for receptor mapping. This facility included an Evans and Sutherland P330 vector terminal coupled to a VAX 785 minicomputer. Software available for the work included commercial modeling software such as ChemX, Gaussian, molecular mechanics (MM2) and in house developed software such as ARCHEM, and parameters for MM2. The facility was used for modeling of muscarinic agonists, such as muscarine and its congeners, pilocarpine, tropine and antagonists such as atropine, quinuclicline, deptropine and others, to determine their conformational and electrostatic properties. From the conformational and energetic investigations of the ligands, bioactive conformations were obtained, which were fitted into the Beers and Reich and Shulman models and used to determine a pharmacophoric pattern common to all the ligands. From the superpositions of the common pharmacophoric patterns a topography of the muscarinic receptor was developed. The derived model of binding and docking to the receptor map, allowed a rational design of new ligands. Keywords: Organophosphates; Drug development; Antidotes.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 1986
- Accession Number
- ADA204531
Entities
People
- Tamara Gund
Organizations
- New Jersey Institute of Technology