Constrained search of conformational hyperspace
- 1 March 1989
- journal article
- conference paper
- Published by Springer Nature in Journal of Computer-Aided Molecular Design
- Vol. 3 (1) , 3-21
- https://doi.org/10.1007/bf01590992
Abstract
We introduce a new method for determining pharmacophore or active site geometries by analysis of the structures of a series of active compounds. The method, constrained search, and the key concepts on which it is based, is described and illustrated by its application to 28 potent inhibitors of angiotensin-converting enzyme (ACE). The data set is one utilized by Mayer et al. [J. Comput.-Aided Mol. Design, 1 (1987) 3–16] to determine a unique geometry for the active site. Our experiment validated the previously reported results, obtained by a systematic search, while reducing the computer time requirement by more than two orders of magnitude. The experiment also identified a previously unrecognized alternative active site geometry for the ACE series.This publication has 12 references indexed in Scilit:
- Three-dimensional structure-activity relationshipsTrends in Pharmacological Sciences, 1988
- Designing novel nicotinic agonists by searching a database of molecular shapesJournal of Computer-Aided Molecular Design, 1987
- A unique geometry of the active site of angiotensin-converting enzyme consistent with structure-activity studiesJournal of Computer-Aided Molecular Design, 1987
- Computer-Aided Drug DesignAnnual Review of Pharmacology and Toxicology, 1987
- The ensemble approach to distance geometry: application to the nicotinic pharmacophoreJournal of Medicinal Chemistry, 1986
- Three‐Dimensional Quantitative Structure‐Activity Relationships I. General Approach to the Pharmacophore Model ValidationQuantitative Structure-Activity Relationships, 1986
- Chain closure with bond angle variationsMacromolecules, 1985
- Recognition of cholinergic agonists by the muscarinic receptor. 1. Acetylcholine and other agonists with the NCCOCC backboneJournal of Medicinal Chemistry, 1983
- The Conformational Parameter in Drug Design: The Active Analog ApproachPublished by American Chemical Society (ACS) ,1979
- Ring Closure and Local Conformational Deformations of Chain MoleculesMacromolecules, 1970