Isolated transmembrane helices arranged across a membrane: computational studies

A computational procedure for predicting the arrangement of an isolated hel ical fragment across a membrane was developed. The procedure places the tra nsmembrane helical segment into a model triple-phase system 'water-octanol- water'; pulls the segment through the membrane, varying its 'global' positi on as a rigid body; optimizes the intrahelical and solvation energies in ea ch global position by 'local' coordinates (dihedral angles of side chains); and selects the lowest energy global position for the segment. The procedu re was applied to 45 transmembrane helices from the photosynthetic reaction center from Rhodopseudomonas viridis, cytochrome c oxidase from Paracoccus denitrificans and bacteriorhodopsin. In two thirds of the helical fragment s considered, the procedure has predicted the vertical shifts of the fragme nts across the membrane with an accuracy of -0.15 +/- 3.12 residues compare d with the experimental data. The accuracy for the remaining 15 fragments w as 2.17 +/- 3.07 residues, which is about half of a helix turn. The procedu re predicts the actual membrane boundaries of transmembrane helical fragmen ts with greater accuracy than existing statistical methods. At the same tim e, the procedure overestimates the tilt values for the helical fragments.