Protein structure determination by exhaustive search of Protein Data Bank derived databases
Open accessAbstract
Parallel sequence and structure alignment tools have become ubiquitous and invaluable at all levels in the study of biological systems. We demonstrate the application and utility of this same parallel search paradigm to the process of protein structure determination, benefitting from the large and growing corpus of known structures. Such searches were previously computationally intractable. Through the method of Wide Search Molecular Replacement, developed here, they can be completed in a few hours with the aide of national-scale federated cyberinfrastructure. By dramatically expanding the range of models considered for structure determination, we show that small (less than 12% structural coverage) and low sequence identity (less than 20% identity) template structures can be identified through multidimensional template scoring metrics and used for structure determination. Many new macromolecular complexes can benefit significantly from such a technique due to the lack of known homologous protein folds or sequences. We demonstrate the effectiveness of the method by determining the structure of a full-length p97 homologue from Trichoplusia ni . Example cases with the MHC/T-cell receptor complex and the EmoB protein provide systematic estimates of minimum sequence identity, structure coverage, and structural similarity required for this method to succeed. We describe how this structure-search approach and other novel computationally intensive workflows are made tractable through integration with the US national computational cyberinfrastructure, allowing, for example, rapid processing of the entire Structural Classification of Proteins protein fragment database.
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Each KpnFepA contains >50% identity to EcoFepA, ensuring a similar protein fold.
“However, each of them contains >50% identity to EcoFepA, ensuring a similar protein fold (25,26).”
From Siderophore-mediated iron acquisition by <i>Klebsiella pneumoniae</i> (2024) · cites this paper as [26]
The Results describe a related p97 example in which proteins have similar architecture, consistent with the general idea that related sequences can have similar structures. The paper does not discuss KpnFepA or EcoFepA, establish their >50% identity, or show that their folds are similar. (LLM, conf=0.81)
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Siderophore-mediated iron acquisition by <i>Klebsiella pneumoniae</i>
Kumar, A., Chakravorty, S., Yang, T., Russo, T. A., Newton, S. M., & Klebba, P. E. (2024) · Journal of Bacteriology · doi:10.1128/jb.00024-24 · Cited by 42 · see citing works
Universal fluorescent sensors of high-affinity iron transport, applied to ESKAPE pathogens
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- Authors
- Stokes-Rees, I., & Sliz, P.
- Affiliations
- Harvard University (US)
- Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115; and
- ORCID
- Stokes-Rees, Ian
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-11-22
- Volume
- 107
- Issue
- 50
- Pages
- 21476-21481
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3003117
- OpenAlex
- W1964889794
- Cited by
- 45
- References
- 40
- Citations by year
- 2025: 1 · 2024: 2 · 2022: 3 · 2021: 1 · 2020: 3 · 2019: 4 · 2018: 2 · 2017: 4 · 2016: 4 · 2015: 2 · 2014: 4 · 2013: 9 · 2012: 5
- FWCI
- 2.36
- 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 (0639193)
- U.S. Department of Energy
- National Institutes of Health
- Office of Science
- National Institute of General Medical Sciences (P01GM062580)
- Topics
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- protein structure determination, molecular replacement, Protein Data Bank, macromolecular complexes, Trichoplusia ni, parallel computing, cyberinfrastructure
- MeSH terms
- Amino Acid Sequence, Animals, Models, Molecular, Molecular Sequence Data, Protein Conformation, Proteins, Sequence Alignment, Sequence Homology, Amino Acid, Computational Biology, Databases, Protein, Mice
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