Estimating the length of transmembrane helices using Z-coordinate predictions.
Zpred2 is an improved version of ZPRED, a predictor for the Z-coordinates of alpha-helical membrane proteins, that is, the distance of the residues from the center of the membrane. Using principal component analysis and a set of neural networks, Zpred2 analyzes data extracted from the amino acid sequence, the predicted topology, and evolutionary profiles. Zpred2 achieves an average accuracy error of 2.18 A (2.17 A when an independent test set is used), an improvement by 15% compared to the previous version. We show that this accuracy is sufficient to enable the predictions of helix lengths with a correlation coefficient of 0.41. As a comparison, two state-of-the-art HMM-based topology prediction methods manage to predict the helix lengths with a correlation coefficient of less than 0.1. In addition, we applied Zpred2 to two other problems, the re-entrant region identification and model validation. Re-entrants were able to be detected with a certain consistency, but not better than with previous approaches, while incorrect models as well as mispredicted helices of transmembrane proteins could be distinguished based on the Z-coordinate predictions.
Papaloukas
Costas
C
Stockholm Bioinformatics Center, Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, SE-106 91 Stockholm, Sweden.
Granseth
Erik
E
Viklund
Håkan
H
Elofsson
Arne
A
D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D016571:Neural Networks, Computer; D025341:Principal Component Analysis; D017433:Protein Structure, Secondary; D012984:Software
D008565:Membrane Proteins