Isolated transmembrane helices arranged across a membrane: Computational studies

Abstract

A computational procedure for predicting the arrangement of an isolated helical fragment across a membrane was developed. The procedure places the transmembrane helical segment into a model triple-phase system 'water-octanol-water'; pulls the segment through the membrane, varying its 'global' position as a rigid body; optimizes the intrahelical and solvation energies in each global position by 'local' coordinates (dihedral angles of side chains); and selects the lowest energy global position for the segment. The procedure 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 fragments considered, the procedure has predicted the vertical shifts of the fragments across the membrane with an accuracy of -0.15 ± 3.12 residues compared with the experimental data. The accuracy for the remaining 15 fragments was 2.17 ± 3.07 residues, which is about half of a helix turn. The procedure predicts the actual membrane boundaries of transmembrane helical fragments with greater accuracy than existing statistical methods. At the same time, the procedure overestimates the tilt values for the helical fragments.