Entropy, Fluctuations, and Disordered Proteins
Entropy should directly reflect the extent of disorder in proteins. By clustering structurally related proteins and studying the multiple-sequence-alignment of the sequences of these clusters, we were able to link between sequence, structure, and disorder information. We introduced several parameter...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-08-01
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| Series: | Entropy |
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| Online Access: | https://www.mdpi.com/1099-4300/21/8/764 |
| _version_ | 1818001567550275584 |
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| author | Eshel Faraggi A. Keith Dunker Robert L. Jernigan Andrzej Kloczkowski |
| author_facet | Eshel Faraggi A. Keith Dunker Robert L. Jernigan Andrzej Kloczkowski |
| author_sort | Eshel Faraggi |
| collection | DOAJ |
| description | Entropy should directly reflect the extent of disorder in proteins. By clustering structurally related proteins and studying the multiple-sequence-alignment of the sequences of these clusters, we were able to link between sequence, structure, and disorder information. We introduced several parameters as measures of fluctuations at a given MSA site and used these as representative of the sequence and structure entropy at that site. In general, we found a tendency for negative correlations between disorder and structure, and significant positive correlations between disorder and the fluctuations in the system. We also found evidence for residue-type conservation for those residues proximate to potentially disordered sites. Mutation at the disorder site itself appear to be allowed. In addition, we found positive correlation for disorder and accessible surface area, validating that disordered residues occur in exposed regions of proteins. Finally, we also found that fluctuations in the dihedral angles at the original mutated residue and disorder are positively correlated while dihedral angle fluctuations in spatially proximal residues are negatively correlated with disorder. Our results seem to indicate permissible variability in the disordered site, but greater rigidity in the parts of the protein with which the disordered site interacts. This is another indication that disordered residues are involved in protein function. |
| first_indexed | 2024-04-14T03:34:51Z |
| format | Article |
| id | doaj.art-a6df9ff5e09e450795f1e343cd53743c |
| institution | Directory Open Access Journal |
| issn | 1099-4300 |
| language | English |
| last_indexed | 2024-04-14T03:34:51Z |
| publishDate | 2019-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Entropy |
| spelling | doaj.art-a6df9ff5e09e450795f1e343cd53743c2022-12-22T02:14:48ZengMDPI AGEntropy1099-43002019-08-0121876410.3390/e21080764e21080764Entropy, Fluctuations, and Disordered ProteinsEshel Faraggi0A. Keith Dunker1Robert L. Jernigan2Andrzej Kloczkowski3Department of Physics, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USADepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USARoy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011, USABattelle Center for Mathematical Medicine, The Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205, USAEntropy should directly reflect the extent of disorder in proteins. By clustering structurally related proteins and studying the multiple-sequence-alignment of the sequences of these clusters, we were able to link between sequence, structure, and disorder information. We introduced several parameters as measures of fluctuations at a given MSA site and used these as representative of the sequence and structure entropy at that site. In general, we found a tendency for negative correlations between disorder and structure, and significant positive correlations between disorder and the fluctuations in the system. We also found evidence for residue-type conservation for those residues proximate to potentially disordered sites. Mutation at the disorder site itself appear to be allowed. In addition, we found positive correlation for disorder and accessible surface area, validating that disordered residues occur in exposed regions of proteins. Finally, we also found that fluctuations in the dihedral angles at the original mutated residue and disorder are positively correlated while dihedral angle fluctuations in spatially proximal residues are negatively correlated with disorder. Our results seem to indicate permissible variability in the disordered site, but greater rigidity in the parts of the protein with which the disordered site interacts. This is another indication that disordered residues are involved in protein function.https://www.mdpi.com/1099-4300/21/8/764protein disorderprotein structureentropyfluctuationsmutations |
| spellingShingle | Eshel Faraggi A. Keith Dunker Robert L. Jernigan Andrzej Kloczkowski Entropy, Fluctuations, and Disordered Proteins Entropy protein disorder protein structure entropy fluctuations mutations |
| title | Entropy, Fluctuations, and Disordered Proteins |
| title_full | Entropy, Fluctuations, and Disordered Proteins |
| title_fullStr | Entropy, Fluctuations, and Disordered Proteins |
| title_full_unstemmed | Entropy, Fluctuations, and Disordered Proteins |
| title_short | Entropy, Fluctuations, and Disordered Proteins |
| title_sort | entropy fluctuations and disordered proteins |
| topic | protein disorder protein structure entropy fluctuations mutations |
| url | https://www.mdpi.com/1099-4300/21/8/764 |
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