A hidden Markov model for prediction transmembrane helices in proteinsequences

Erik L.L. Sonnhammer, Gunnar von Heijne, Anders Stærmose Krogh

    Research output: Chapter in Book/Report/Conference proceedingArticle in proceedingsResearchpeer-review


    A novel method to model and predict the location and orientation of alpha helices in membrane-spanning proteins is presented. It is based on a hidden Markov model (HMM) with an architecture that corresponds closely to the biological system. The model is cyclic with 7 types of states for helix core, helix caps on either side, loop on the cytoplasmic side, two loops for the non-cytoplasmic side, and a globular domain state in the middle of each loop. The two loop paths on the non-cytoplasmic side are used to model short and long loops separately, which corresponds biologically to the two known different membrane insertions mechanisms. The close mapping between the biological and computational states allows us to infer which parts of the model architecture are important to capture the information that encodes the membrane topology, and to gain a better understanding of the mechnaisms and constraints involved. Models were estimated both by maximum likelihood and a discriminative method, and a method for reassignment of the membrane helix boundaries were developed. In a cross validated test on single sequences, our transmembrane HMM, TMHMM, correctly predicts the entire topology for 77% of the sequences in a standard dataset of 83 proteins with known topology. The same accuracy was achieved on a larger dataset of 160 proteins. These results compare favourably with existing methods.
    Original languageEnglish
    Title of host publicationProceedings of the Sixth International Conference on Intelligent Systems for Molecular Biology
    Place of PublicationMenlo Park
    PublisherAAAI Press
    Publication date1998
    Publication statusPublished - 1998
    EventSixth InternationalConference on Intelligent Systems for Molecular Biology - Montreal, Canada
    Duration: 1 Jan 1998 → …


    ConferenceSixth InternationalConference on Intelligent Systems for Molecular Biology
    CityMontreal, Canada
    Period01/01/1998 → …

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