Topological Predictions for Integral Membrane Channel and CarrierProteins

摘要

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>S OSUI. 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 topologicalpredictions for any subdivision (class, subclass, superfamily, family,subfamily, or any combination of these) of the Transporter ClassificationDatabase (TCDB; ) and examined the following subclasses:α-type channel proteins (TC subclasses 1.A and 1.E), secretedporeforming toxins (TC subclass 1.C) and secondary carriers (subclass 2.A).Histograms 3 were generated for each of these subclasses, and the results wereanalyzed according to subclass, family and protein. The results provide anupdate of topological predictions for integral membrane transport proteins aswell as guides for the development of more reliable topological predictionprograms, taking family-specific characteristics into account.