Two modes of membrane binding by H-Ras were observed in previous simulations [17].

(a) An approximately perpendicular orientation of the catalytic domain with respect to the membrane plane. This conformation, which we refer to as conf1, was frequently sampled during GDP-H-ras simulations [17]. (b) Semi-parallel orientation of the catalytic domain with respect to the membrane plane, which we refer to here as conf2. These two conformations were used as starting structures for the current simulations. Helices 4 and 5, as well as the bound nucleotide, are labeled. The canonical switches SI and SII are at the bottom of the image surrounding the nucleotide. Also shown in space-filling representation are side chains of the HVR along with Arg128 and Arg135 on helix 4, as well as the three lipid modifications (two palmitoyls at positions 181 and 184 and a farnesyl at position 186).