Molecular modeling of the (S)-ABA binding site of the receptor involved in the induction of freezing tolerance: A hypothetical receptor model

Abstract

Molecular modeling was used to compare abscisic acid (ABA) analogs to rationalize reported structure-activity relationships based on the induction of freezing tolerance in bromegrass (Bromus inermis Leyss.) cell culture. A modified version of the active analog approach was employed with (S)-ABA used as the standard to which other compounds were superimposed. Common conformations that present similar three-dimensional steric and electronic patterns were identified through conformational searches. From this analysis, a hypothetical model for the putative (S)-ABA receptor was constructed with the following features. The ring is in the pseudochair conformation with an axial side chain. The C-1′ has the same absolute stereochemistry as (S)-ABA. The model suggests that discrimination between (S)-ABA, phaseic acid, and (R)-ABA is due to the presence of an ether bridge or a methyl group below the C-2′ of (S)-ABA, in a region proposed to be occupied by the receptor. The side chain is syn with the ring and positioned approximately above the 2′-carbon of the ring. The model serves as a working hypothesis for testing receptor requirements and can be used to direct future analog studies.