Long membrane helices and short loops predicted less accurately

Low-resolution experiments suggest that most membrane helices span over 17-25 residues and that most loops between two helices are longer than 15 residues. Both constraints have been used explicitly in the development of prediction methods. Here, we compared the largest possible sequence-unique data sets from high- and low-resolution experiments. For the high-resolution data, we found that only half of the helices fall into the expected length interval and that half of the loops were shorter than 10 residues. We compared the accuracy of detecting short loops and long helices for 28 advanced and simple prediction methods: All methods predicted short loops less accurately than longer ones. In particular, loops shorter than 7 residues appeared to be very difficult to detect by current methods. Similarly, all methods tended to be more accurate for longer than for shorter helices. However, helices with more than 32 residues were predicted less accurately than all other helices. Our findings may suggest particular strategies for improving predictions of membrane helices.