Exploring hydrophilic sequence space to search for uncharted foldable proteins by AlphaFold2
Proteins typically fold into unique three-dimensional structures largely driven by interactions between hydrophobic amino acids. This understanding has helped improve our knowledge of protein folding. However, recent research has shown an exception to this idea, demonstrating that specific threonine...
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| Format: | Article |
| Language: | English |
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The Biophysical Society of Japan
2025-03-01
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| Series: | Biophysics and Physicobiology |
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| Online Access: | https://doi.org/10.2142/biophysico.bppb-v22.0005 |
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| author | Naoki Tomita Hiroki Onoda Leonard M. G. Chavas George Chikenji |
| author_facet | Naoki Tomita Hiroki Onoda Leonard M. G. Chavas George Chikenji |
| author_sort | Naoki Tomita |
| collection | DOAJ |
| description | Proteins typically fold into unique three-dimensional structures largely driven by interactions between hydrophobic amino acids. This understanding has helped improve our knowledge of protein folding. However, recent research has shown an exception to this idea, demonstrating that specific threonine-rich peptides have a strong tendency to form β-hairpin structures, even in the highly hydrophilic amino acid sequences. This finding suggests that the hydrophilic amino acid sequence space still leaves room for exploring foldable amino acid sequences. In this study, we conducted a systematic exploration of the repetitive amino acid sequence space by AlphaFold2 (AF2), with a focus on sequences composed exclusively of hydrophilic residues, to investigate their potential for adopting unique structures. As a result, the sequence space exploration suggested that several repetitive threonine-rich sequences adopt distinctive conformations and these conformational shapes can be influenced by the length of the sequence unit. Moreover, the analysis of structural dataset suggested that threonine contributes to the structural stabilization by forming non-polar atom packing that tolerates unsatisfied hydrogen bonds, and while also supporting other residues in forming hydrogen bonds. Our findings will broaden the horizons for the discovery of foldable amino acid sequences consisting solely of hydrophilic residues and help us clarify the unknown mechanisms of protein structural stabilization. |
| format | Article |
| id | doaj-art-e92e121624c542fba24a507080b08099 |
| institution | OA Journals |
| issn | 2189-4779 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | The Biophysical Society of Japan |
| record_format | Article |
| series | Biophysics and Physicobiology |
| spelling | doaj-art-e92e121624c542fba24a507080b080992025-08-20T02:03:06ZengThe Biophysical Society of JapanBiophysics and Physicobiology2189-47792025-03-012210.2142/biophysico.bppb-v22.0005Exploring hydrophilic sequence space to search for uncharted foldable proteins by AlphaFold2Naoki Tomita0Hiroki Onoda1Leonard M. G. Chavas2George Chikenji3Department of Applied Physics, Graduate School of Engineering, Nagoya University, Nagoya, Aichi 464-8602, JapanNagoya University Synchrotron Radiation Research Center, Nagoya University, Nagoya, Aichi 464-8603, JapanDepartment of Applied Physics, Graduate School of Engineering, Nagoya University, Nagoya, Aichi 464-8602, JapanDepartment of Applied Physics, Graduate School of Engineering, Nagoya University, Nagoya, Aichi 464-8602, JapanProteins typically fold into unique three-dimensional structures largely driven by interactions between hydrophobic amino acids. This understanding has helped improve our knowledge of protein folding. However, recent research has shown an exception to this idea, demonstrating that specific threonine-rich peptides have a strong tendency to form β-hairpin structures, even in the highly hydrophilic amino acid sequences. This finding suggests that the hydrophilic amino acid sequence space still leaves room for exploring foldable amino acid sequences. In this study, we conducted a systematic exploration of the repetitive amino acid sequence space by AlphaFold2 (AF2), with a focus on sequences composed exclusively of hydrophilic residues, to investigate their potential for adopting unique structures. As a result, the sequence space exploration suggested that several repetitive threonine-rich sequences adopt distinctive conformations and these conformational shapes can be influenced by the length of the sequence unit. Moreover, the analysis of structural dataset suggested that threonine contributes to the structural stabilization by forming non-polar atom packing that tolerates unsatisfied hydrogen bonds, and while also supporting other residues in forming hydrogen bonds. Our findings will broaden the horizons for the discovery of foldable amino acid sequences consisting solely of hydrophilic residues and help us clarify the unknown mechanisms of protein structural stabilization.https://doi.org/10.2142/biophysico.bppb-v22.0005threoninealphafold2hydrophilic amino acid sequence |
| spellingShingle | Naoki Tomita Hiroki Onoda Leonard M. G. Chavas George Chikenji Exploring hydrophilic sequence space to search for uncharted foldable proteins by AlphaFold2 Biophysics and Physicobiology threonine alphafold2 hydrophilic amino acid sequence |
| title | Exploring hydrophilic sequence space to search for uncharted foldable proteins by AlphaFold2 |
| title_full | Exploring hydrophilic sequence space to search for uncharted foldable proteins by AlphaFold2 |
| title_fullStr | Exploring hydrophilic sequence space to search for uncharted foldable proteins by AlphaFold2 |
| title_full_unstemmed | Exploring hydrophilic sequence space to search for uncharted foldable proteins by AlphaFold2 |
| title_short | Exploring hydrophilic sequence space to search for uncharted foldable proteins by AlphaFold2 |
| title_sort | exploring hydrophilic sequence space to search for uncharted foldable proteins by alphafold2 |
| topic | threonine alphafold2 hydrophilic amino acid sequence |
| url | https://doi.org/10.2142/biophysico.bppb-v22.0005 |
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