THE USE OF THE GRID PROGRAM IN THE 3-D QSAR ANALYSIS OF A SERIES OF CALCIUM-CHANNEL AGONISTS

The use of GRID in the 3-D QSAR analysis of a series of calcium-channel agonists is described. Partial least-squares analysis of GRID maps showing the interaction energy between an alkyl hydroxyl probe and a series of agonists in 3-D space generated a predictive quantitative model of the variation of biological activity. The macroscopic descriptors CLOGP and CMR were included in the analysis, and the importance of appropriate block scaling is highlighted. The discussion highlights the interpretation of the resulting regression maps, and the steric, electrostatic, lipophilic, and hydrogen-bonding preferences of the calcium-channel receptor are identified.