title: Reliability of nine programs of topological predictions and their application to integral membrane channel and carrier proteins.
abstract: We evaluated topological predictions for nine different programs, HMMTOP, TMHMM, SVMTOP, DAS, SOSUI, TOPCONS, PHOBIUS, MEMSAT-SVM (hereinafter referred to as MEMSAT), and SPOCTOPUS. These programs were first evaluated using four large topologically well-defined families of secondary transporters, and the three best programs were further evaluated using topologically more diverse families of channels and carriers. In the initial studies, the order of accuracy was: SPOCTOPUS > MEMSAT > HMMTOP > TOPCONS > PHOBIUS > TMHMM > SVMTOP > DAS > SOSUI. Some families, such as the Sugar Porter Family (2.A.1.1) of the Major Facilitator Superfamily (MFS; TC #2.A.1) and the Amino Acid/Polyamine/Organocation (APC) Family (TC #2.A.3), were correctly predicted with high accuracy while others, such as the Mitochondrial Carrier (MC) (TC #2.A.29) and the K(+) transporter (Trk) families (TC #2.A.38), were predicted with much lower accuracy. For small, topologically homogeneous families, SPOCTOPUS and MEMSAT were generally most reliable, while with large, more diverse superfamilies, HMMTOP often proved to have the greatest prediction accuracy. We next developed a novel program, TM-STATS, that tabulates HMMTOP, SPOCTOPUS or MEMSAT-based topological predictions for any subdivision (class, subclass, superfamily, family, subfamily, or any combination of these) of the Transporter Classification Database (TCDB; www.tcdb.org) and examined the following subclasses: α-type channel proteins (TC subclasses 1.A and 1.E), secreted pore-forming toxins (TC subclass 1.C) and secondary carriers (subclass 2.A). Histograms were generated for each of these subclasses, and the results were analyzed according to subclass, family and protein. The results provide an update of topological predictions for integral membrane transport proteins as well as guides for the development of more reliable topological prediction programs, taking family-specific characteristics into account.
authors.affiliation: Department of Molecular Biology, University of California at San Diego, La Jolla, Calif., USA.
authors.forename: Abhinay
authors.initials: A
authors.lastname: Reddy
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Cho
authors.forename: Sam
authors.initials: S
authors.lastname: Ling
authors.forename: Vamsee
authors.initials: V
authors.lastname: Reddy
authors.forename: Maksim
authors.initials: M
authors.lastname: Shlykov
authors.forename: Milton H
authors.initials: MH
authors.lastname: Saier
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D019295:Computational Biology / Q000379:methods*; D007473:Ion Channels / Q000737:chemistry* / Q000378:metabolism; D012984:Software
chemical_list: D002352:Carrier Proteins; D007473:Ion Channels