Molecular mechanics investigation on conformational flexibility of 14 beta steroids in drug-receptor interactions

The interaction between two 14 beta steroids being still unsynthesized and a model receptor binding site is theoretically studied by a molecular mechanics scheme. Both compounds containing seven-membered rings in the 17 beta position are found to form stable hydrogen bonds to the receptor and can be attributed to be potential inhibitors of the Na+,K+-ATPase activity. Substantial steroid conformational changes necessary for an efficient receptor binding are calculated to reduce the interaction energy by only 10 kJ mol-1. Therefore, alterations in steroid structure should be generally taken into consideration in the investigation of steroid-receptor interactions.