Environment specific substitution tables improve membrane protein alignment.
MOTIVATION: Membrane proteins are both abundant and important in cells, but the small number of solved structures restricts our understanding of them. Here we consider whether membrane proteins undergo different substitutions from their soluble counterparts and whether these can be used to improve...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2011
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| _version_ | 1797096175204040704 |
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| author | Hill, JR Kelm, S Shi, J Deane, C |
| author_facet | Hill, JR Kelm, S Shi, J Deane, C |
| author_sort | Hill, JR |
| collection | OXFORD |
| description | MOTIVATION: Membrane proteins are both abundant and important in cells, but the small number of solved structures restricts our understanding of them. Here we consider whether membrane proteins undergo different substitutions from their soluble counterparts and whether these can be used to improve membrane protein alignments, and therefore improve prediction of their structure. RESULTS: We construct substitution tables for different environments within membrane proteins. As data is scarce, we develop a general metric to assess the quality of these asymmetric tables. Membrane proteins show markedly different substitution preferences from soluble proteins. For example, substitution preferences in lipid tail-contacting parts of membrane proteins are found to be distinct from all environments in soluble proteins, including buried residues. A principal component analysis of the tables identifies the greatest variation in substitution preferences to be due to changes in hydrophobicity; the second largest variation relates to secondary structure. We demonstrate the use of our tables in pairwise sequence-to-structure alignments (also known as 'threading') of membrane proteins using the FUGUE alignment program. On average, in the 10-25% sequence identity range, alignments are improved by 28 correctly aligned residues compared with alignments made using FUGUE's default substitution tables. Our alignments also lead to improved structural models. AVAILABILITY: Substitution tables are available at: http://www.stats.ox.ac.uk/proteins/resources. |
| first_indexed | 2024-03-07T04:38:19Z |
| format | Journal article |
| id | oxford-uuid:d0bf29d9-ed1b-43ee-ad57-3ff56ee9d320 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:38:19Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:d0bf29d9-ed1b-43ee-ad57-3ff56ee9d3202022-03-27T07:52:12ZEnvironment specific substitution tables improve membrane protein alignment.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d0bf29d9-ed1b-43ee-ad57-3ff56ee9d320EnglishSymplectic Elements at Oxford2011Hill, JRKelm, SShi, JDeane, C MOTIVATION: Membrane proteins are both abundant and important in cells, but the small number of solved structures restricts our understanding of them. Here we consider whether membrane proteins undergo different substitutions from their soluble counterparts and whether these can be used to improve membrane protein alignments, and therefore improve prediction of their structure. RESULTS: We construct substitution tables for different environments within membrane proteins. As data is scarce, we develop a general metric to assess the quality of these asymmetric tables. Membrane proteins show markedly different substitution preferences from soluble proteins. For example, substitution preferences in lipid tail-contacting parts of membrane proteins are found to be distinct from all environments in soluble proteins, including buried residues. A principal component analysis of the tables identifies the greatest variation in substitution preferences to be due to changes in hydrophobicity; the second largest variation relates to secondary structure. We demonstrate the use of our tables in pairwise sequence-to-structure alignments (also known as 'threading') of membrane proteins using the FUGUE alignment program. On average, in the 10-25% sequence identity range, alignments are improved by 28 correctly aligned residues compared with alignments made using FUGUE's default substitution tables. Our alignments also lead to improved structural models. AVAILABILITY: Substitution tables are available at: http://www.stats.ox.ac.uk/proteins/resources. |
| spellingShingle | Hill, JR Kelm, S Shi, J Deane, C Environment specific substitution tables improve membrane protein alignment. |
| title | Environment specific substitution tables improve membrane protein alignment. |
| title_full | Environment specific substitution tables improve membrane protein alignment. |
| title_fullStr | Environment specific substitution tables improve membrane protein alignment. |
| title_full_unstemmed | Environment specific substitution tables improve membrane protein alignment. |
| title_short | Environment specific substitution tables improve membrane protein alignment. |
| title_sort | environment specific substitution tables improve membrane protein alignment |
| work_keys_str_mv | AT hilljr environmentspecificsubstitutiontablesimprovemembraneproteinalignment AT kelms environmentspecificsubstitutiontablesimprovemembraneproteinalignment AT shij environmentspecificsubstitutiontablesimprovemembraneproteinalignment AT deanec environmentspecificsubstitutiontablesimprovemembraneproteinalignment |