SToMP / JSUBST
17/06/2011
Full working title: Substitution Tables of Membrane Proteins
Type: Software development, data analysis
Scope: DPhil sub-project (Oxford, UK)
Start date: October 2007
End date: January 2011
Authors:
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-Sebastian Kelm (development & data analysis, 2007-11)
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-Jamie R. Hill (data analysis, 2010-2011)
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-Jiye Shi (industrial supervisor)
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-Charlotte M. Deane (academic supervisor)
Aim:
Create a set of environment-specific substitution tables of membrane proteins as a first step towards modelling their structure. These tables should include information specific to the different membrane layers, i.e. the inner and outer parts of the lipid bilayer, as well as information about the water-soluble parts of membrane proteins. Comparisons to tables for globular proteins should provide some insight into the molecular evolution of membrane proteins. Feeding the tables into programmes such as FUGUE will allow more accurate alignment of a membrane protein structure to a sequence. Structure prediction software, such as MEDELLER, can now use such tables to decide which parts of a template structure may be copied. Tables were built using my JSUBST program.
Project progress:
June 2011
Paper published: Environment Specific Substitution Tables Improve Membrane Protein Alignment
January 2011
We have submitted a paper about SToMP.
With the paper, we are releasing JSUBST and a set of SToMP tables to the public. These tables are, so far, proof-of-concept tables. Given a lot of time, these could potentially become much better still.
October 2010
SToMP tables can be generated from any set of PDB files within one day. Generating the tables themselves from the data is actually a matter of seconds/minutes. It is thus a simple matter to customise the structural environments for which one needs substitution tables.
October 2008
Statistical analysis of the tables show the expected behaviour, in most cases.
One example: “Lipid-exposed residues in transmembrane helices are very different from water-exposed residues in soluble or even membrane proteins.”
Another example: “Residues in contact with the polar head groups of the membrane lipids are less different from water-exposed residues than are the residues in contact with the hydrophobic lipid tail groups.”
I have presented a poster about this project at the ISMB 2008 conference and the associated 3Dsig satellite meeting in Toronto, Canada.
Done:
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-Pipeline to generate the data needed to make substitution tables (uses iMembrane)
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-JSUBST, the Java programme which generates the tables themselves from the above data (modified re-implementation of SUBST by Kenji Mizuguchi)
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-Analysis pipeline, which runs some simple statistical analyses on a set of substitution tables
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-Created membrane-specific modelling software MEDELLER, using the SToMP tables
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-More detailed analysis of the substitution tables, in collaboration with Jamie R. Hill
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-Proof-of-concept sequence-to-structure alignment (threading) using SToMP
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-Structure prediction with MEDELLER based on SToMP/FUGUE alignments
Web links:
