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Open Access Research article

AlignHUSH: Alignment of HMMs using structure and hydrophobicity information

Oruganty Krishnadev12 and Narayanaswamy Srinivasan1*

Author Affiliations

1 Molecular Biophysics Unit Indian Institute of Science, Bangalore 560012, India

2 A318, Biochemistry and Molecular Biology Department, 120 East Green Street, Athens, GA 30602, USA

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BMC Bioinformatics 2011, 12:275  doi:10.1186/1471-2105-12-275

Published: 5 July 2011

Abstract

Background

Sensitive remote homology detection and accurate alignments especially in the midnight zone of sequence similarity are needed for better function annotation and structural modeling of proteins. An algorithm, AlignHUSH for HMM-HMM alignment has been developed which is capable of recognizing distantly related domain families The method uses structural information, in the form of predicted secondary structure probabilities, and hydrophobicity of amino acids to align HMMs of two sets of aligned sequences. The effect of using adjoining column(s) information has also been investigated and is found to increase the sensitivity of HMM-HMM alignments and remote homology detection.

Results

We have assessed the performance of AlignHUSH using known evolutionary relationships available in SCOP. AlignHUSH performs better than the best HMM-HMM alignment methods and is observed to be even more sensitive at higher error rates. Accuracy of the alignments obtained using AlignHUSH has been assessed using the structure-based alignments available in BaliBASE. The alignment length and the alignment quality are found to be appropriate for homology modeling and function annotation. The alignment accuracy is found to be comparable to existing methods for profile-profile alignments.

Conclusions

A new method to align HMMs has been developed and is shown to have better sensitivity at error rates of 10% and above when compared to other available programs. The proposed method could effectively aid obtaining clues to functions of proteins of yet unknown function.

A web-server incorporating the AlignHUSH method is available at http://crick.mbu.iisc.ernet.in/~alignhush/ webcite