Rapid and sensitive protein similarity searches

Lipman, David J.; Pearson, William R.

doi:10.1126/science.2983426

Cited by 4,033Genomics and Phylogenetic StudiesAlgorithms and Data CompressionFractal and DNA sequence analysis

Rapid and sensitive protein similarity searches

Lipman, David J., Pearson, William R.·1985·Science

DOI 10.1126/science.2983426

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Abstract

An algorithm was developed which facilitates the search for similarities between newly determined amino acid sequences and sequences already available in databases. Because of the algorithm's efficiency on many microcomputers, sensitive protein database searches may now become a routine procedure for molecular biologists. The method efficiently identifies regions of similar sequence and then scores the aligned identical and differing residues in those regions by means of an amino acid replacability matrix. This matrix increases sensitivity by giving high scores to those amino acid replacements which occur frequently in evolution. The algorithm has been implemented in a computer program designed to search protein databases very rapidly. For example, comparison of a 200-amino-acid sequence to the 500,000 residues in the National Biomedical Research Foundation library would take less than 2 minutes on a minicomputer, and less than 10 minutes on a microcomputer (IBM PC).

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The seed-and-extend paradigm has been the standard approach to short-read alignment for over 30 years and has proven very effective for highly accurate reads.
“The seed-and-extend paradigm for full-genome nucleotide alignment has been the standard approach to short-read alignment for over 30 years, and has proven very effective for highly accurate reads [24, 57, 58].”
From <tt>SAFARI</tt> : pangenome alignment of ancient DNA using purine/pyrimidine encodings (2025) · cites this paper as [57]

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<tt>SAFARI</tt> : pangenome alignment of ancient DNA using purine/pyrimidine encodings
Rubin, J., van Waaij, J., Kraft, L., Sirén, J., Sackett, P. W., & Renaud, G. (2025) · NAR Genomics and Bioinformatics · doi:10.1093/nargab/lqaf170 · Cited by 1 · see citing works
“The seed-and-extend paradigm for full-genome nucleotide alignment has been the standard approach to short-read alignment for over 30 years, and has proven very effective for highly accurate reads [ 24 , 57 , 58 ].”
Méthodes d'analyse comparée des pangénomes procaryotes : explorer la diversité génomique inter-espèces pour une meilleure compréhension du métabolisme
Arnoux, J. (2026) · Thèse de doctorat, Université Paris-Saclay / PPanGGOLiN · doi:10.70675/eee354d9zf63dz48ebz9444zd1809f8fb74d

Authors: Lipman, D. J., & Pearson, W. R.
Affiliations: National Institutes of Health (US)
University of Virginia (US)
ORCID: Lipman, David J.
Pearson, William R.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1985-03-22
Volume: 227
Issue: 4693
Pages: 1435-1441
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.2983426
OpenAlex: W2029195137
Cited by: 4,033
References: 23
Citations by year: 2026: 19 · 2025: 30 · 2024: 37 · 2023: 35 · 2022: 34 · 2021: 48 · 2020: 44 · 2019: 44 · 2018: 57 · 2017: 43 · 2016: 38 · 2015: 45 · 2014: 64 · 2013: 59 · 2012: 51
FWCI: 108.05
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (2s07rr005431-31)
National Center for Research Resources (SO7RR05431)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
Physical Sciences › Computer Science › Artificial Intelligence › Algorithms and Data Compression
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fractal and DNA sequence analysis
Keywords: sequence alignment, protein database searching, microcomputer implementation
MeSH terms: Cyclic AMP, Amino Acid Sequence, Angiotensinogen, Animals, Bunyaviridae, Cattle, Computers, Cytochrome c Group, Biological Evolution, Humans, Information Systems, Microcomputers, Nucleoproteins, Probability, Protein Kinases, Protein Precursors, Proteins, Software, Viral Proteins, Rats

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Rapid and sensitive protein similarity searches

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