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| Content Provider | Royal Society of Chemistry (RSC) |
|---|---|
| Author | Jayadev, C. Srinivasan, N. Mudgal, R. Abhinandan, K. R. Sowdhamini, R. Sandhya, S. |
| Copyright Year | 2012 |
| Abstract | Over the past two decades, many ingenious efforts have been made in protein remote homology detection. Because homologous proteins often diversify extensively in sequence, it is challenging to demonstrate such relatedness through entirely sequence-driven searches. Here, we describe a computational method for the generation of ‘protein-like’ sequences that serves to bridge gaps in protein sequence space. Sequence profile information, as embodied in a position-specific scoring matrix of multiply aligned sequences of bona fide family members, serves as the starting point in this algorithm. The observed amino acid propensity and the selection of a random number dictate the selection of a residue for each position in the sequence. In a systematic manner, and by applying a ‘roulette-wheel’ selection approach at each position, we generate parent family-like sequences and thus facilitate an enlargement of sequence space around the family. When generated for a large number of families, we demonstrate that they expand the utility of natural intermediately related sequences in linking distant proteins. In 91% of the assessed examples, inclusion of designed sequences improved fold coverage by 5–10% over searches made in their absence. Furthermore, with several examples from proteins adopting folds such as TIM, globin, lipocalin and others, we demonstrate that the success of including designed sequences in a database positively sensitized methods such as PSI-BLAST and Cascade PSI-BLAST and is a promising opportunity for enormously improved remote homology recognition using sequence information alone. |
| Starting Page | 2076 |
| Ending Page | 2084 |
| Page Count | 9 |
| File Format | HTM / HTML PDF |
| ISSN | 1742206X |
| Volume Number | 8 |
| Issue Number | 8 |
| Journal | Molecular BioSystems |
| DOI | 10.1039/c2mb25113b |
| Language | English |
| Publisher | Royal Society of Chemistry |
| Access Restriction | Open |
| Subject Keyword | Globin FIDE Lipocalin Position weight matrix Algorithm BLAST Protein Sequence homology Sequence space |
| Content Type | Text |
| Resource Type | Article |
| Subject | Molecular Biology Biotechnology |
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