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

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