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Cited by 15Protein Structure and DynamicsAdvanced Fluorescence Microscopy TechniquesEnzyme Structure and Function

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AlphaFold2 and RoseTTAFold predict posttranslational modifications. Chromophore formation in GFP-like proteins

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Hartley, Sophia M., Tiernan, Kelly A., Ahmetaj, Gjina, Cretu, Adriana, Zhuang, Yan, Zimmer, Marc·2022·PLOS ONE
DOI 10.1371/journal.pone.0267560PMC PMC9202861

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Abstract

AlphaFold2 and RoseTTAfold are able to predict, based solely on their sequence whether GFP-like proteins will post-translationally form a chromophore (the part of the protein responsible for fluorescence) or not. Their training has not only taught them protein structure and folding, but also chemistry. The structures of 21 sequences of GFP-like fluorescent proteins that will post-translationally form a chromophore and of 23 GFP-like non-fluorescent proteins that do not have the residues required to form a chromophore were determined by AlphaFold2 and RoseTTAfold. The resultant structures were mined for a series of geometric measurements that are crucial to chromophore formation. Statistical analysis of these measurements showed that both programs conclusively distinguished between chromophore forming and non-chromophore forming proteins. A clear distinction between sequences capable of forming a chromophore and those that do not have the residues required for chromophore formation can be obtained by examining a single measurement—the RMSD of the overlap of the central alpha helices of the crystal structure of S65T GFP and the AlphaFold2 determined structure. Only 10 of the 578 GFP-like proteins in the pdb have no chromophore, yet when AlphaFold2 and RoseTTAFold are presented with the sequences of 44 GFP-like proteins that are not in the pdb they fold the proteins in such a way that one can unequivocally distinguish between those that can and cannot form a chromophore.

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Figures

Fig 1 The cyclization-dehydration-oxidation pathway for chromophore formation. [26] Structure I is known as the immature precyclized form of the protein. The tight-turn distance depicted in structure I was measured for all sequences and is presented in S1 Data. Structure V shows the fully formed mature chromophore (green).
Fig 1 The cyclization-dehydration-oxidation pathway for chromophore formation. [26] Structure I is known as the immature precyclized form of the protein. The tight-turn distance depicted in structure I was measured for all sequences and is presented in S1 Data. Structure V shows the fully formed mature chromophore (green).CC BY · PubMed Central
Fig 2 RMSD overlap of the α-helix of the 1EMA-crystal structure with the α-helix of 1EMA as determined by AlphaFold2 for GFP-like proteins that will form a chromophore (SYG) and those that do not (no SYG).
Fig 2 RMSD overlap of the α-helix of the 1EMA-crystal structure with the α-helix of 1EMA as determined by AlphaFold2 for GFP-like proteins that will form a chromophore (SYG) and those that do not (no SYG).CC BY · PubMed Central

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Metadata

Authors
Hartley, S. M., Tiernan, K. A., Ahmetaj, G., Cretu, A., Zhuang, Y., & Zimmer, M.
Affiliations
Connecticut College (US)
Corresponding author
Zimmer, Marc
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2022-06-16
Volume
17
Issue
6
Pages
e0267560
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0267560
PMC
PMC9202861
OpenAlex
W4282969955
Cited by
15
References
5
Citations by year
2026: 4 · 2025: 2 · 2024: 2 · 2023: 5 · 2022: 2
FWCI
0.90
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
Keywords
AlphaFold2, RoseTTAFold, chromophore formation, green fluorescent protein, protein structure prediction, RMSD, geometric measurement
MeSH terms
Fluorescence, Luminescent Proteins, Protein Processing, Post-Translational, Green Fluorescent Proteins

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CoChat. (2026). Citation check: AlphaFold2 and RoseTTAFold predict posttranslational modifications. Chromophore formation in GFP-like proteins. https://app.cochat.ai/papers/10.1371/journal.pone.0267560
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Hartley, S. M., Tiernan, K. A., Ahmetaj, G., Cretu, A., Zhuang, Y., & Zimmer, M. (2022). AlphaFold2 and RoseTTAFold predict posttranslational modifications. Chromophore formation in GFP-like proteins. PLOS ONE. https://doi.org/10.1371/journal.pone.0267560