Conformational Analysis of Charged Homo-Polypeptides
Many proteins have intrinsically disordered regions (IDRs), which are often characterized by a high fraction of charged residues with polyampholytic (i.e., mixed charge) or polyelectrolytic (i.e., uniform charge) characteristics. Polyelectrolytic IDRs include consecutive positively charged Lys or Ar...
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| Format: | Article |
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MDPI AG
2023-02-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/2/363 |
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| author | Lavi S. Bigman Yaakov Levy |
| author_facet | Lavi S. Bigman Yaakov Levy |
| author_sort | Lavi S. Bigman |
| collection | DOAJ |
| description | Many proteins have intrinsically disordered regions (IDRs), which are often characterized by a high fraction of charged residues with polyampholytic (i.e., mixed charge) or polyelectrolytic (i.e., uniform charge) characteristics. Polyelectrolytic IDRs include consecutive positively charged Lys or Arg residues (K/R repeats) or consecutive negatively charged Asp or Glu residues (D/E repeats). In previous research, D/E repeats were found to be about five times longer than K/R repeats and to be much more common in eukaryotes. Within these repeats, a preference is often observed for E over D and for K over R. To understand the greater prevalence of D/E over K/R repeats and the higher abundance of E and K, we simulated the conformational ensemble of charged homo-polypeptides (polyK, polyR, polyD, and polyE) using molecular dynamics simulations. The conformational preferences and dynamics of these polyelectrolytic polypeptides change with changes in salt concentration. In particular, polyD and polyE are more sensitive to salt than polyK and polyR, as polyD and polyE tend to adsorb more divalent cations, which leads to their having more compact conformations. We conclude with a discussion of biophysical explanations for the relative abundance of charged amino acids and particularly for the greater abundance of D/E repeats over K/R repeats. |
| first_indexed | 2024-03-11T09:06:16Z |
| format | Article |
| id | doaj.art-c185680c2a1f47aca238a2e921ccf2e9 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T09:06:16Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-c185680c2a1f47aca238a2e921ccf2e92023-11-16T19:24:09ZengMDPI AGBiomolecules2218-273X2023-02-0113236310.3390/biom13020363Conformational Analysis of Charged Homo-PolypeptidesLavi S. Bigman0Yaakov Levy1Department of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot 7610001, IsraelDepartment of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot 7610001, IsraelMany proteins have intrinsically disordered regions (IDRs), which are often characterized by a high fraction of charged residues with polyampholytic (i.e., mixed charge) or polyelectrolytic (i.e., uniform charge) characteristics. Polyelectrolytic IDRs include consecutive positively charged Lys or Arg residues (K/R repeats) or consecutive negatively charged Asp or Glu residues (D/E repeats). In previous research, D/E repeats were found to be about five times longer than K/R repeats and to be much more common in eukaryotes. Within these repeats, a preference is often observed for E over D and for K over R. To understand the greater prevalence of D/E over K/R repeats and the higher abundance of E and K, we simulated the conformational ensemble of charged homo-polypeptides (polyK, polyR, polyD, and polyE) using molecular dynamics simulations. The conformational preferences and dynamics of these polyelectrolytic polypeptides change with changes in salt concentration. In particular, polyD and polyE are more sensitive to salt than polyK and polyR, as polyD and polyE tend to adsorb more divalent cations, which leads to their having more compact conformations. We conclude with a discussion of biophysical explanations for the relative abundance of charged amino acids and particularly for the greater abundance of D/E repeats over K/R repeats.https://www.mdpi.com/2218-273X/13/2/363intrinsically disordered proteinspolyelectrolytesD/E repeatsK/R repeatsmolecular dynamics simulations |
| spellingShingle | Lavi S. Bigman Yaakov Levy Conformational Analysis of Charged Homo-Polypeptides Biomolecules intrinsically disordered proteins polyelectrolytes D/E repeats K/R repeats molecular dynamics simulations |
| title | Conformational Analysis of Charged Homo-Polypeptides |
| title_full | Conformational Analysis of Charged Homo-Polypeptides |
| title_fullStr | Conformational Analysis of Charged Homo-Polypeptides |
| title_full_unstemmed | Conformational Analysis of Charged Homo-Polypeptides |
| title_short | Conformational Analysis of Charged Homo-Polypeptides |
| title_sort | conformational analysis of charged homo polypeptides |
| topic | intrinsically disordered proteins polyelectrolytes D/E repeats K/R repeats molecular dynamics simulations |
| url | https://www.mdpi.com/2218-273X/13/2/363 |
| work_keys_str_mv | AT lavisbigman conformationalanalysisofchargedhomopolypeptides AT yaakovlevy conformationalanalysisofchargedhomopolypeptides |