Steroid molecular properties influence the biophysical state of steroid-containing membranes

WENZ J.J.

Granada

Congreso; XV Congress of the Spanish Biophysical Society; 2015

Sociedad Biophyica de España (SBE)

     The effectsof steroids on the biophysical state of membranes were investigated byanalyzing the ordering, rigidifying, condensing and/or raft promoting activityon membranes of a library of 82 steroids. Based on the documented membraneactivity, steroids were classified by means of a categorical variable [1] into three possible categories: disrupters, neutralsor promoters of such activity. All steroids were subjected to geometry optimizationusing the semi-empirical procedure AM1 and 245 molecular descriptors were next computed[2] on the low energy conformations. After the removal ofthe invariant descriptors, the remaining 93 were correlated with membraneactivity through principal component analysis (PCA) [3] and mean contrasting.     Employingthree principal components (71 % of explained variance), the PCA score plotshowed two well-defined clusters of steroids reflecting similarities in theirmolecular properties. After the identification and counting of cluster´s members(Table) it was found that disrupter steroids represent around 94 % of thepopulation of cluster 1. On the other hand, the 100 % of the promoter and the95 % of the neutral steroids were located in cluster 2. Distribution of steroids in clusters according totheir activity on membranes. Category of % in cluster % in category   membrane activity cluster 1 cluster 2 cluster 1 cluster 2   Disrupter steroids 93.8 13.6 62.5 37.5 100 Neutral steroids 6.2 28.8 5.0 95.0 100 Promoter steroids 0 57.6 0 100 100 100 100         Collectively,these findings indicate that steroids having similarities in some molecular propertieshave similar activity on membranes, and that some of steroid molecularproperties influence the biophysical state of steroid-containing membranes. Bymeans of a thorough analysis of the PCA scores and loading it was found thatthe area, log P, volume, mass, refractivity, number of rotatable bonds andpolarizability are the most relevant properties in determining the effect ofsteroids on membranes. A mean contrasting test revealed significant differences(p<0.001) in all of these properties among the promoter and the disrupter populations,agreeing and reinforcing the preceding conclusions.