Molecular properties of steroids involved in their effects on the biophysical state of membranes

WENZ J.J.

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES

ELSEVIER SCIENCE BV

Lugar: Maryland; Año: 2015 vol. 1848 p. 2448 - 2459

0005-2736

The activity of steroids on membranes wasstudied in relation to their ordering, rigidifying, condensing and/or raftpromoting ability. The structures of 82 steroids were modeled by asemi-empirical procedure (AM1) and 245 molecular descriptors were next computedon the optimized energy conformations. Principal component analysis, meancontrasting and logistic regression were used to correlate the molecular propertieswith 212 cases of documented activities. It was possible to group steroids basedon their properties and activities, indicating that steroids having similarmolecular properties have similar activities on membranes. Steroids having highvalues of area, partition coefficient, volume, number of rotatable bonds, molarrefractivity, polarizability or mass displayed ordering, rigidifying,condensing and/or raft promoting activity on membranes higher than those steroidshaving low values in such molecular properties. After a variable selectionprocedure circumventing correlation problems among descriptors, area and log Pwere found as the most relevant properties in governing and predicting the activityof steroids on membranes. A logistic regression model as a function of the areaand log P of the steroids is proposed, which is able to predict correctly the92.5 % of the cases. A rationale of the findings is discussed.