Motivation: Transmembrane (TM) proteins that form α-helix bundles constitute approximately 50% of contemporary drug targets. Yet, it is difficult to determine their high-resolution (< 4 Å) structures. Some TM proteins yield more easily to structure determination using cryo electron microscopy (cryo-EM), though this technique most often results in lower resolution structures, precluding an unambiguous assignment of TM amino acid sequences to the helices seen in the structure. We present computational tools for assigning the TM segments in the protein's sequence to the helices seen in cryo-EM structures. Results: The method examines all feasible TM helix assignments and ranks each one based on a score function that was derived from loops in the structures of soluble α-helix bundles. A set of the most likely assignments is then suggested. We tested the method on eight TM chains of known structures, such as bacteriorhodopsin and the lactose permease. Our results indicate that many assignments can be rejected at the outset, since they involve the connection of pairs of remotely placed TM helices. The correct assignment received a high score, and was ranked highly among the remaining assignments. For example, in the lactose permease, which contains 12 TM helices, most of which are connected by short loops, only 12 out of 479 million assignments were found to be feasible, and the native one was ranked first. Availability: The program and the non-redundant set of protein structures used here are available at http://www.cs.tau.ac.il/~angela.