From Protein Structure to Function with Bioinformatics.pdf

4 Membrane Protein Structure Prediction 103Table 4.4 Machine learning-based beta-barrel TM topology predictors. MSA: Topology predictionsmade using multiple sequence alignments. HGA: Suitable for whole genome analysisMethod URL Algorithm FeaturesB2TMRhttp://gpcr.biocomp. NNMSAunibo.it/predictors/TMBETA-NET http://psfs.cbrc.jp/ NNMSA, HGAtmbeta-net/HMM-B2TMR http://gpcr.biocomp. HMMMSAunibo.it/predictors/PROFtmbhttp://www.rostlab. HMMHGAorg/services/PROFtmb/PRED-TMBB http://biophysics.biol. HMMHGAuoa.gr/PRED-TMBB/TMBETA-SVM http://tmbeta-svm. SVMHGAcbrc.jp/TMB-Hunt2http://bmbpcu36.leeds.ac.uk/HMM + SVM HGAfor discriminating between globular and TM proteins. To do so requires the methodto be specially trained for this process, and that the program is available as a standalonepackage as web-based predictors are unsuitable for such large-scale submissions.A number of methods which are suitable for whole genome analysis ofalpha-helical and beta-barrel TM proteins are shown in Tables 4.3 and 4.4. In general,error rates are minimised by prior filtering to remove signal and transit peptidesusing methods such as SignalP and TargetP, since many globular proteins with suchsignal sequences are frequently predicted as single spanning TM proteins. Currently,the best methods are capable of error rates of less than 1% for alpha-helical TM proteins(Jones 2007) and less than 6% for beta-barrel TM proteins (Park et al. 2005).The results of applying an alpha-helical TM protein discriminator to a number ofproteomes are shown in Fig. 4.6.4.6.4 Data Sets, Homology, Accuracy and Cross-ValidationA key element when constructing any prediction method is the use of a high qualitydata set for both training and validation purposes. Extracting a training set fromavailable databases requires a large amount of work and requires a number of criticaldecisions to be made. As an example in the case of TM proteins, searches of databasessuch as the PDB using the keyword ‘transmembrane’ will return both genomicallyencoded TM proteins as well as TM proteins that are not native, such as entry1BH1 – a bilayer disrupting peptide found in bee venom – and 1CII, a bacterial