Thanks Geoff,
The bottom line seems to be that Jalview code treats Threonine as not hydrophobic. This is a bug if the intention is to match the diagram and matrix published to support the method. For example column 68 of uniref50.fa, which is conserved T and !hydrophobic. Jim is of the opinion that we should correct this, but keep the default behaviour backwards compatible with past versions. A question on thresholding the conservation calculation: The AMAS paper refers to ignoring counts representing less than N% of the column [the 'N%' is a missing image in the html version] but doesn't state the choice of N as far as I can see. Jalview has N=3. Is it possible to view the original code to compare? A question on treatment of gaps: "gaps are normally given all properties ... so that aligned positions that contain a gap are assigned a low conservation value" Does this not give a high rather than a low value? Or rather, have no effect on property conservation (logical OR) but prevent negative conservation (of absence of property)? That seems to be the effect, but it is asymmetric with regard to presence or absence of a property. Jalview also applies a threshold requiring less than 25% gaps in a column to compute any conservation. This doesn't seem to be mentioned in the paper or Jalview help. I would be interested to know if it is from the original implementation or an addition. Thanks, Mungo Mungo Carstairs Jalview Computational Scientist The Barton Group Division of Computational Biology School of Life Sciences University of Dundee, Dundee, Scotland, UK. www.jalview.org<http://www.jalview.org/> www.compbio.dundee.ac.uk<http://www.compbio.dundee.ac.uk/> ________________________________ From: Geoffrey Barton (Staff) Sent: 02 November 2016 11:03:37 To: Mungo Carstairs (Staff); Jalview Development List; Geoffrey Barton (Staff) Subject: Re: [Jalview-dev] Is Threonine hydrophobic? Hi Mungo, The point I was making is that we always follow the work of W. Taylor in this since his analysis (published in 1986 in J. Theor. Biol.) is the most complete simplified consideration of amino acid properties. It is derived by projecting amino acid subsitution matrices into 2D space and then applying biophysical knowledge to the resulting plot (which is dominated by size and hydrophobicity). https://www.ncbi.nlm.nih.gov/pubmed/3461222. A few other people have written on this subject since then - e.g.: http://i122server.vu-wien.ac.at/pop/Kosiol_website/pdfs/KosiolGoldmanButtimoreJTB2004.pdf http://peds.oxfordjournals.org/content/12/9/707.full but these have not got much traction in the community. As I said before, Threonine is classed as BOTH Hydrophobic and Polar. It is not the only amino acid like this. Many text books (and the online resources you point at) take a simplistic view that only allows amino acids to have a single property. For example, they typically class Lysine (K) as "Charged". This hides the fact that Lysine has a long aliphatic side chain and is often seen in largely hydrophobic environments with the end of the side chain exposed to solvent or in a salt-bridge. Simple text book definitions also usually ignore size which is one of the most important biophysical properties of an amino acid. When I teach about amino acid properties, the first thing I have to explain is that the view that amino acid side chains have a single physico-chemical property is too simplistic. I have a powerpoint lecture on this topic if you are interested. In Jalview we could take the view that we should provide people with a range of different classifications of the amino acids. I would prefer that we stick with the one that we know from long experience is a reasonable and general representation. I hope this helps? Geoff. On 02/11/2016 09:11, Mungo Carstairs (Staff) wrote: Hi Geoff, Thanks, I do know what a Venn diagram represents! Also the page I linked to does show multiple properties for amino acids. The question was whether Threonine should be classed as hydrophobic (in which case the diagram needs amended) or not (in which case Jalview code needs amended). >From a Google search on amino acid properties, these pages class T as not >hydrophobic: http://www.sigmaaldrich.com/life-science/metabolomics/learning-center/amino-acid-reference-chart.html http://p53.iarc.fr/AAProperties.aspx https://www.mcb.ucdavis.edu/courses/bis102/aaprop.html https://www.thermofisher.com/uk/en/home/life-science/protein-biology/protein-biology-learning-center/protein-biology-resource-library/pierce-protein-methods/amino-acid-physical-properties.html# http://www.proteinstructures.com/Structure/Structure/amino-acids.html https://en.wikipedia.org/wiki/Amino_acid#Physicochemical_properties_of_amino_acids http://www.biology.arizona.edu/biochemistry/problem_sets/aa/Threonine.html These class T as hydrophobic: http://www.russelllab.org/aas/ https://www.ncbi.nlm.nih.gov/Class/Structure/aa/aa_explorer.cgi Question remains, which is it (for Jalview conservation purposes at least)? thanks mungo Mungo Carstairs Jalview Computational Scientist The Barton Group Division of Computational Biology School of Life Sciences University of Dundee, Dundee, Scotland, UK. www.jalview.org<http://www.jalview.org/> www.compbio.dundee.ac.uk<http://www.compbio.dundee.ac.uk/> ________________________________ From: [email protected]<mailto:[email protected]> <[email protected]><mailto:[email protected]> on behalf of Geoff Barton <[email protected]><mailto:[email protected]> Sent: 01 November 2016 17:38:40 To: Jalview Development List Subject: Re: [Jalview-dev] Is Threonine hydrophobic? Hi Mungo, The point of the Venn Diagram is that it shows amino acids to have multiple properties. Threonine sits in the middle of the diagram and has the properties: Polar, Hydrophobic, Small. Simple classifications like the one you link to do not capture the fact that amino acids exhibit multiple physico-chemical properties. Rob Russell developed the definitive online resource for amino acid properties: See http://www.russelllab.org/aas/ Geoff. On 01/11/2016 12:43, Mungo Carstairs (Staff) wrote: The Venn Diagram (included in Jalview Help as Amino Acid Properties) says that it is. Jalview code, and other reference sources, say it is hydrophilic. e.g. http://p53.iarc.fr/AAProperties.aspx Does the diagram need an update? Thanks, mungo Mungo Carstairs Jalview Computational Scientist The Barton Group Division of Computational Biology School of Life Sciences University of Dundee, Dundee, Scotland, UK. www.jalview.org<http://www.jalview.org/> www.compbio.dundee.ac.uk<http://www.compbio.dundee.ac.uk/> The University of Dundee is a registered Scottish Charity, No: SC015096 _______________________________________________ Jalview-dev mailing list [email protected]<mailto:[email protected]> http://www.compbio.dundee.ac.uk/mailman/listinfo/jalview-dev -- Geoff Barton | Professor of Bioinformatics | Head of Division of Computational Biology School of Life Sciences | University of Dundee, Scotland, UK | [email protected]<mailto:[email protected]> Tel: +44 1382 385860 | www.compbio.dundee.ac.uk<http://www.compbio.dundee.ac.uk> | twitter: @gjbarton The University of Dundee is registered Scottish charity: No.SC015096 The University of Dundee is a registered Scottish Charity, No: SC015096 -- Geoff Barton | Professor of Bioinformatics | Head of Division of Computational Biology School of Life Sciences | University of Dundee, Scotland, UK | [email protected]<mailto:[email protected]> Tel: +44 1382 385860 | www.compbio.dundee.ac.uk<http://www.compbio.dundee.ac.uk> | twitter: @gjbarton The University of Dundee is registered Scottish charity: No.SC015096 The University of Dundee is a registered Scottish Charity, No: SC015096
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