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On the reliability and the limits of inference of amino acid sequence alignments.


ABSTRACT:

Motivation

Alignments are correspondences between sequences. How reliable are alignments of amino acid sequences of proteins, and what inferences about protein relationships can be drawn? Using techniques not previously applied to these questions, by weighting every possible sequence alignment by its posterior probability we derive a formal mathematical expectation, and develop an efficient algorithm for computation of the distance between alternative alignments allowing quantitative comparisons of sequence-based alignments with corresponding reference structure alignments.

Results

By analyzing the sequences and structures of 1 million protein domain pairs, we report the variation of the expected distance between sequence-based and structure-based alignments, as a function of (Markov time of) sequence divergence. Our results clearly demarcate the 'daylight', 'twilight' and 'midnight' zones for interpreting residue-residue correspondences from sequence information alone.

Supplementary information

Supplementary data are available at Bioinformatics online.

SUBMITTER: Rajapaksa S 

PROVIDER: S-EPMC9235515 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

On the reliability and the limits of inference of amino acid sequence alignments.

Rajapaksa Sandun S   Sumanaweera Dinithi D   Lesk Arthur M AM   Allison Lloyd L   Stuckey Peter J PJ   Garcia de la Banda Maria M   Abramson David D   Konagurthu Arun S AS  

Bioinformatics (Oxford, England) 20220601 Suppl 1


<h4>Motivation</h4>Alignments are correspondences between sequences. How reliable are alignments of amino acid sequences of proteins, and what inferences about protein relationships can be drawn? Using techniques not previously applied to these questions, by weighting every possible sequence alignment by its posterior probability we derive a formal mathematical expectation, and develop an efficient algorithm for computation of the distance between alternative alignments allowing quantitative com  ...[more]

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