Abstract
Protein tertiary structure is important information in various areas of biological research, however, the experimental cost associated with structure determination is high, and computational prediction methods have been developed to facilitate a more economical approach. Currently, template-based modeling methods are considered to be the most practical because the resulting predicted structures are often accurate, provided an appropriate template protein is available. During the first stage of template-based modeling, sensitive homology detection is essential for accurate structure prediction. However, sufficient structural models cannot always be obtained due to a lack of quality in the sequence alignment generated by a homology detection program. Therefore, an automated method that detects remote homologs accurately and generates appropriate alignments for accurate structure prediction is needed. In this paper, we propose an algorithm for suitable alignment generation using an intermediate sequence search for use with template-based modeling. We used intermediate sequence search for remote homology detection and intermediate sequences for alignment generation of remote homologs. We then evaluated the proposed method by comparing the sensitivity and selectivity of homology detection. Furthermore, based on the accuracy of the predicted structure model, we verify the accuracy of the alignments generated by our method. We demonstrate that our method generates more appropriate alignments for template-based modeling, especially for remote homologs. All source codes are available at https://github.com/shuichiro-makigaki/agora.
Highlights
Proteins are key molecules in biology, biochemistry, and pharmaceutical sciences
We developed an alignment generation algorithm suited for accurate template-based modeling based on intermediate sequence search (ISS) for remote homology detection
In the alignment generation phase, we proposed a method that extended the hit region detected by the ISS, and used multiple pairwise alignments between intermediate sequences
Summary
Proteins are key molecules in biology, biochemistry, and pharmaceutical sciences. A protein’s structure often has a strong correlation with its function. The structure of a protein is an important piece of information in biological research. Protein structures can be determined experimentally using X-ray crystallography or nuclear magnetic resonance spectroscopy, and protein structures determined in this way are registered to, and accessible in the online Protein Databank (PDB) [1]. Despite vast improvements in the available experimental methods for protein structure determination, the speed at which amino acid sequences can be revealed has surpassed our ability to ascertain the corresponding structure. Protein structure prediction, that is, the use
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