Computational Tools for Interpreting Ion Channel pH-Dependence.
Activity in many biological systems is mediated by pH, involving proton titratable groups with pKas in the relevant pH range. Experimental analysis of pH-dependence in proteins focusses on particular sidechains, often with mutagenesis of histidine, due to its pKa near to neutral pH. The key question...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4411139?pdf=render |
| _version_ | 1818943232337248256 |
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| author | Ivan Sazanavets Jim Warwicker |
| author_facet | Ivan Sazanavets Jim Warwicker |
| author_sort | Ivan Sazanavets |
| collection | DOAJ |
| description | Activity in many biological systems is mediated by pH, involving proton titratable groups with pKas in the relevant pH range. Experimental analysis of pH-dependence in proteins focusses on particular sidechains, often with mutagenesis of histidine, due to its pKa near to neutral pH. The key question for algorithms that predict pKas is whether they are sufficiently accurate to effectively narrow the search for molecular determinants of pH-dependence. Through analysis of inwardly rectifying potassium (Kir) channels and acid-sensing ion channels (ASICs), mutational effects on pH-dependence are probed, distinguishing between groups described as pH-coupled or pH-sensor. Whereas mutation can lead to a shift in transition pH between open and closed forms for either type of group, only for pH-sensor groups does mutation modulate the amplitude of the transition. It is shown that a hybrid Finite Difference Poisson-Boltzmann (FDPB) - Debye-Hückel continuum electrostatic model can filter mutation candidates, providing enrichment for key pH-coupled and pH-sensor residues in both ASICs and Kir channels, in comparison with application of FDPB alone. |
| first_indexed | 2024-12-20T07:24:03Z |
| format | Article |
| id | doaj.art-155df605f34444ff92da836f9d1d4c63 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T07:24:03Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-155df605f34444ff92da836f9d1d4c632022-12-21T19:48:34ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01104e012529310.1371/journal.pone.0125293Computational Tools for Interpreting Ion Channel pH-Dependence.Ivan SazanavetsJim WarwickerActivity in many biological systems is mediated by pH, involving proton titratable groups with pKas in the relevant pH range. Experimental analysis of pH-dependence in proteins focusses on particular sidechains, often with mutagenesis of histidine, due to its pKa near to neutral pH. The key question for algorithms that predict pKas is whether they are sufficiently accurate to effectively narrow the search for molecular determinants of pH-dependence. Through analysis of inwardly rectifying potassium (Kir) channels and acid-sensing ion channels (ASICs), mutational effects on pH-dependence are probed, distinguishing between groups described as pH-coupled or pH-sensor. Whereas mutation can lead to a shift in transition pH between open and closed forms for either type of group, only for pH-sensor groups does mutation modulate the amplitude of the transition. It is shown that a hybrid Finite Difference Poisson-Boltzmann (FDPB) - Debye-Hückel continuum electrostatic model can filter mutation candidates, providing enrichment for key pH-coupled and pH-sensor residues in both ASICs and Kir channels, in comparison with application of FDPB alone.http://europepmc.org/articles/PMC4411139?pdf=render |
| spellingShingle | Ivan Sazanavets Jim Warwicker Computational Tools for Interpreting Ion Channel pH-Dependence. PLoS ONE |
| title | Computational Tools for Interpreting Ion Channel pH-Dependence. |
| title_full | Computational Tools for Interpreting Ion Channel pH-Dependence. |
| title_fullStr | Computational Tools for Interpreting Ion Channel pH-Dependence. |
| title_full_unstemmed | Computational Tools for Interpreting Ion Channel pH-Dependence. |
| title_short | Computational Tools for Interpreting Ion Channel pH-Dependence. |
| title_sort | computational tools for interpreting ion channel ph dependence |
| url | http://europepmc.org/articles/PMC4411139?pdf=render |
| work_keys_str_mv | AT ivansazanavets computationaltoolsforinterpretingionchannelphdependence AT jimwarwicker computationaltoolsforinterpretingionchannelphdependence |