Conformational analysis of phorbol esters at a simulated membrane/water interface

The conformation at a simulated membrane/water interface of four distinct phorbol esters, selected for their vastly different tumor-promoting potency, was predicted by a modification of the usual computing approach for the conformational analysis of macromolecules. In the modified procedure, the transfer energy of each part of the molecule in either a hydrophobic or hydrophilic domain was taken into account in order to define the orientation of the molecule at the simulated interface. The results of this study are compatible with known tensioactive properties of these phorbol esters, and may help to explain differences in their biological potency by the relative facility of their insertion in lipid bilayers.