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

Sandun Rajapaksa, Dinithi Sumanaweera, Arthur M. Lesk, Lloyd Allison, Peter J. Stuckey, Maria Garcia De La Banda, David Abramson, Arun S. Konagurthu

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)I255-I263
StatePublished - Jul 1 2022

All Science Journal Classification (ASJC) codes

  • Statistics and Probability
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Computational Theory and Mathematics
  • Computational Mathematics


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