A Method to Identify Protein Sequences That Fold into a Known Three-Dimensional Structure
Abstract
The inverse protein folding problem, the problem of finding which amino acid sequences fold into a known three-dimensional (3D) structure, can be effectively attacked by finding sequences that are most compatible with the environments of the residues in the 3D structure. The environments are described by: (i) the area of the residue buried in the protein and inaccessible to solvent; (ii) the fraction of side-chain area that is covered by polar atoms (O and N); and (iii) the local secondary structure. Examples of this 3D profile method are presented for four families of proteins: the globins, cyclic AMP (adenosine 3′,5′-monophosphate) receptor-like proteins, the periplasmic binding proteins, and the actins. This method is able to detect the structural similarity of the actins and 70- kilodalton heat shock proteins, even though these protein families share no detectable sequence similarity.
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The principle that tertiary structure models aid structural template retrieval has long been understood and is the basis of protein threading.
“Of course, this principle has been well understood for some time, and is the basis of protein threading (45,46), but the ease and speed with which a rough candidate model can be generated for a query sequence has the potential to accelerate and improve the sensitivity of structural template searches.”
From Ultrafast end-to-end protein structure prediction enables high-throughput exploration of uncharacterised proteins (2020) · cites this paper as [45]
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- Authors
- Bowie, J. U., Lüthy, R., & Eisenberg, D.
- Affiliations
- University of California, Los Angeles (US)
- Venue
- Science
- Published
- 1991-07-12
- Volume
- 253
- Issue
- 5016
- Pages
- 164-170
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W4246356731
- Cited by
- 2,851
- References
- 50
- Citations by year
- 2026: 84 · 2025: 128 · 2024: 117 · 2023: 128 · 2022: 162 · 2021: 111 · 2020: 101 · 2019: 120 · 2018: 96 · 2017: 102 · 2016: 105 · 2015: 78 · 2014: 97 · 2013: 77 · 2012: 60
- FWCI
- 24.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- protein sequence identification, buried surface area, side chain polarity, globin, periplasmic binding protein, actin
- MeSH terms
- Actins, Algorithms, Amino Acid Sequence, Animals, Carrier Proteins, Myoglobin, Protein Conformation, Proteins, Receptors, Cyclic AMP, Structure-Activity Relationship, Molecular Structure, Escherichia coli Proteins, Periplasmic Binding Proteins
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