Predicting the topology of transmembrane helical proteins using mean burial propensity and a hidden-Markov-model-based method.

TitlePredicting the topology of transmembrane helical proteins using mean burial propensity and a hidden-Markov-model-based method.
Publication TypeJournal Article
Year of Publication2003
AuthorsZhou, H, Zhou Y
JournalProtein science : a publication of the Protein Society
Volume12
Pagination1547-55
Date Published2003 Jul
Abstract

Helices in membrane spanning regions are more tightly packed than the helices in soluble proteins. Thus, we introduce a method that uses a simple scale of burial propensity and a new algorithm to predict transmembrane helical (TMH) segments and a positive-inside rule to predict amino-terminal orientation. The method (the topology predictor of transmembrane helical proteins using mean burial propensity [THUMBUP]) correctly predicted the topology of 55 of 73 proteins (or 75%) with known three-dimensional structures (the 3D helix database). This level of accuracy can be reached by MEMSAT 1.8 (a 200-parameter model-recognition method) and a new HMM-based method (a 111-parameter hidden Markov model, UMDHMM(TMHP)) if they were retrained with the 73-protein database. Thus, a method based on a physiochemical property can provide topology prediction as accurate as those methods based on more complicated statistical models and learning algorithms for the proteins with accurately known structures. Commonly used HMM-based methods and MEMSAT 1.8 were trained with a combination of the partial 3D helix database and a 1D helix database of TMH proteins in which topology information were obtained by gene fusion and other experimental techniques. These methods provide a significantly poorer prediction for the topology of TMH proteins in the 3D helix database. This suggests that the 1D helix database, because of its inaccuracy, should be avoided as either a training or testing database. A Web server of THUMBUP and UMDHMM(TMHP) is established for academic users at http://www.smbs.buffalo.edu/phys_bio/service.htm. The 3D helix database is also available from the same Web site.

Pub Med Link

http://www.ncbi.nlm.nih.gov/pubmed/12824500?dopt=Abstract

Alternate JournalProtein Sci.
Citekey12824500