Tertiary alphabet for the observable protein structural universe
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Significance: Proteins fold into intricate 3D structures, determined by their amino acid sequences. Different proteins can fold into drastically different structures, and the space of all possible structures appears hopelessly complex. However, this is precisely the space that needs to be described to understand how sequence encodes structure. In this paper, we decompose the set of known protein structures into standard reusable building blocks, which we call tertiary structural motifs (TERMs). Strikingly, we find that only ∼600 TERMs describe 50% of the known protein structural universe at sub-Angstrom resolution. Furthermore, we find the natural utilization of TERMs gives us a means of uncovering sequence–structure relationships. These insights can be harnessed for protein structure prediction, protein design, and other applications.
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The selected motifs in many cases resemble canonical secondary structure packing patterns and are privileged because they contain a much greater density of favourable side-chain interactions with the target than the rest of the designs.
“These motifs, which in many cases resemble canonical secondary structure packing patterns14, are privileged because they contain a much greater density of favourable side-chain interactions with the target than the rest of the designs.”
From Design of protein-binding proteins from the target structure alone (2022) · cites this paper as [14]
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- Authors
- Mackenzie, C. O., Zhou, J., & Grigoryan, G.
- Affiliations
- Dartmouth College (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-11-03
- Volume
- 113
- Issue
- 47
- Pages
- E7438-E7447
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5127300
- OpenAlex
- W2548003600
- Cited by
- 72
- References
- 76
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 7 · 2023: 8 · 2022: 13 · 2021: 12 · 2020: 7 · 2019: 5 · 2018: 6 · 2017: 4
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (DMR1534246, MCB1517032, CNS-1205521)
- 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 › RNA and protein synthesis mechanisms
- Keywords
- structural degeneracy, sequence-structure mapping, sequence variation, structural coverage, protein structure prediction, protein interfaces, metal coordination, water binding, Protein Data Bank
- MeSH terms
- Algorithms, Amino Acid Sequence, Models, Molecular, Magnetic Resonance Spectroscopy, Protein Conformation, Proteins, Computational Biology, Databases, Protein
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