The relation between the divergence of sequence and structure in proteins.
Open accessAbstract
Homologous proteins have regions which retain the same general fold and regions where the folds differ. For pairs of distantly related proteins (residue identity approximately 20%), the regions with the same fold may comprise less than half of each molecule. The regions with the same general fold differ in structure by amounts that increase as the amino acid sequences diverge. The root mean square deviation in the positions of the main chain atoms, delta, is related to the fraction of mutated residues, H, by the expression: delta(A) = 0.40 e1.87H.
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The two most critical issues in homology modeling are the degree of similarity between the target sequence and the templates and the reliability of the alignment.
“The two most critical issues in homology modeling are the degree of similarity between the target sequence and the templates and the reliability of the alignment, two aspects that are intrinsically interconnected (60).”
From Structural and Functional Characterization of the Aryl Hydrocarbon Receptor Ligand Binding Domain by Homology Modeling and Mutational Analysis (2007) · cites this paper as [60]
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- Authors
- Chothia, C., & Lesk, A. M.
- ORCID
- Lesk, A.M.
- Venue
- The EMBO Journal
- Published
- 1986-04-01
- Volume
- 5
- Issue
- 4
- Pages
- 823-826
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1166865
- OpenAlex
- W1508885706
- Cited by
- 2,458
- References
- 28
- Citations by year
- 2026: 61 · 2025: 56 · 2024: 44 · 2023: 66 · 2022: 62 · 2021: 52 · 2020: 56 · 2019: 59 · 2018: 74 · 2017: 67 · 2016: 64 · 2015: 67 · 2014: 67 · 2013: 100 · 2012: 96
- FWCI
- 8.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM25435)
- 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
- sequence-structure relationship, protein folding, homologous proteins, sequence divergence, structural divergence, RMSD, main-chain conformation, distant homologs
- MeSH terms
- Amino Acid Sequence, Animals, Humans, Mutation, Protein Conformation, Proteins, Structure-Activity Relationship
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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