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A hidden Markov model for predicting transmembrane helices in protein sequences (1998)
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| Venue: | In Proceedings of the 6th International Conference on Intelligent Systems for Molecular Biology (ISMB |
| Citations: | 372 - 9 self |
BibTeX
@INPROCEEDINGS{Sonnhammer98ahidden,
author = {Erik L. L. Sonnhammer},
title = {A hidden Markov model for predicting transmembrane helices in protein sequences},
booktitle = {In Proceedings of the 6th International Conference on Intelligent Systems for Molecular Biology (ISMB},
year = {1998},
pages = {175--182},
publisher = {AAAI Press}
}
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Abstract
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 mechanisms 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 sequencesin 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.
Keyphrases
hidden markov model protein sequence transmembrane helix non-cytoplasmic side known topology loop path helix cap membrane topology transmembrane hmm maximum likelihood single sequence computational state discriminative method model architecture different membrane insertion biological system cytoplasmic side close mapping alpha helix standard dataset entire topology membrane spanning protein membrane helix boundary helix core long loop globular domain state novel method
