Fig. 1.

Ab initio folding protocol with long-range interactions. Interactions can be predicted from sequence information using a database of TMH pairs of known structure (Fig. S1) or can be inferred from experiments (see Materials and Methods). Once an interaction is selected, the two helices connected through space by that interaction are inserted and folded in the membrane. Adjacent individual TMHs are then randomly selected and folded in the membrane by Monte-Carlo fragment insertion sampling. After all TMHs are assembled in the membrane, the initial chain break is closed.