AlphaFold Protein Structure Database for Sequence-Independent Molecular Replacement
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Abstract
Crystallographic phasing recovers the phase information that is lost during a diffraction experiment. Molecular replacement is a commonly used phasing method for crystal structures in the protein data bank. In one form it uses a protein sequence to search a structure database to find suitable templates for phasing. However, sequence information is not always available, such as when proteins are crystallized with unknown binding partner proteins or when the crystal is of a contaminant. The recent development of AlphaFold published the predicted protein structures for every protein from twenty distinct species. In this work, we tested whether AlphaFold-predicted E. coli protein structures were accurate enough to enable sequence-independent phasing of diffraction data from two crystallization contaminants of unknown sequence. Using each of more than 4000 predicted structures as a search model, robust molecular replacement solutions were obtained, which allowed the identification and structure determination of YncE and YadF. Our results demonstrate the general utility of the AlphaFold-predicted structure database with respect to sequence-independent crystallographic phasing.
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AF2 models are increasingly used in X-ray crystallographic molecular replacement and phasing.
“AF2 models have also been increasingly used during molecular replacement and phasing of X-ray diffraction data obtained from protein crystals76–79”
From The power and pitfalls of AlphaFold2 for structure prediction beyond rigid globular proteins (2024) · cites this paper as [77]
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- Authors
- Chai, L., Zhu, P., Chai, J., Pang, C., Andi, B., McSweeney, S., Shanklin, J., & Liu, Q.
- Affiliations
- Brookhaven National Laboratory (US)
- Corresponding author
- Liu, Qun
- Venue
- Crystals
- Publisher
- MDPI AG
- Published
- 2021-10-12
- Volume
- 11
- Issue
- 10
- Pages
- 1227
- ISSN
- 2073-4352 (ISSN-L)
- OpenAlex
- W3207828527
- Cited by
- 15
- References
- 40
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 7 · 2022: 2
- FWCI
- 0.83
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Crystals (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Energy (KC0401040, DE‐SC0012704, KC0304000, KP1607011, DOE KC0304000, SC0012704., P30GM133893)
- National Institutes of Health (DE-SC0012704)
- Office of Science (KC0401040, DE-SC-0012704, SC0012704, KP1607011)
- National Institute of General Medical Sciences (GM107462, R01GM107462, P30GM133893)
- Basic Energy Sciences (DE- SC0012704, KC0401040, DOE KC0304000, SC0012704, KC0304000)
- Biological and Environmental Research (KC0401040, DE-SC0012704, KP1607011)
- Laboratory Directed Research and Development (DE-SC0012704)
- Brookhaven National Laboratory (SC0012704, P30 GM133893, DE- SC0012704, LDRD 22-008, GM107462)
- Topics
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Chemistry › Inorganic Chemistry › Crystal structures of chemical compounds
- Keywords
- AlphaFold, crystallographic phasing, protein structure prediction, Escherichia coli proteins
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