Molecular Mechanics Investigation on Side-Chain Conformations of a 17α-Ethyl-17β-hydroxy Steroid with Regard to Receptor Binding

Abstract

Energetically favourable conformations for simultaneous intramolecular rotations of both the 17 α ethyl side chain and the 17 β hydroxyl group of a model steroid are calculated by MM2 molecular mechanics. In accordance with recent IR and NMR interpretations, the 17α substituent is found to preferably adopt conformations which may sterically hinder the formation of hydrogen bonds between the steroidal 17β oxygen atom and the receptor protein. Furthermore, the 17a ethyl substitution is computed to influence the D-ring conformation and to alter the location of the 17β oxygen function by 28 pm in space.