A Hidden Markov Model for Predicting Transmembrane Helices in Protein Sequences

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, ...

• Type: Conference
• Year: 1998
• Where: ISMB
• Authors: Erik L. L. Sonnhammer, Gunnar von Heijne, Anders Krogh
• Keywords: Computational Biology, Hidden Markov Model, ISMB 1998, Membrane Insertions Mechanisms, Model