Is Threonine hydrophobic?

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

The University of Dundee is a registered Scottish Charity, No: SC015096

···

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
www.compbio.dundee.ac.uk

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.

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
www.compbio.dundee.ac.uk

The University of Dundee is a registered Scottish Charity, No: SC015096

_______________________________________________
Jalview-dev mailing list
[Jalview-dev@jalview.org](mailto:Jalview-dev@jalview.org)
[http://www.compbio.dundee.ac.uk/mailman/listinfo/jalview-dev](http://www.compbio.dundee.ac.uk/mailman/listinfo/jalview-dev)

The University of Dundee is a registered Scottish Charity, No: SC015096

···

On 01/11/2016 12:43, Mungo Carstairs (Staff) wrote:

-- 
Geoff Barton | Professor of Bioinformatics | Head of Division of Computational Biology   
School of Life Sciences | University of Dundee, Scotland, UK | [g.j.barton@dundee.ac.uk](mailto:g.j.barton@dundee.ac.uk) 
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 

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
www.compbio.dundee.ac.uk


From: jalview-dev-bounces@jalview.org jalview-dev-bounces@jalview.org on behalf of Geoff Barton gjbarton@dundee.ac.uk
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

The University of Dundee is a registered Scottish Charity, No: SC015096

_______________________________________________
Jalview-dev mailing list
[Jalview-dev@jalview.org](mailto:Jalview-dev@jalview.org)
[http://www.compbio.dundee.ac.uk/mailman/listinfo/jalview-dev](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 | [g.j.barton@dundee.ac.uk](mailto:g.j.barton@dundee.ac.uk) 
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

The University of Dundee is a registered Scottish Charity, No: SC015096

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
www.compbio.dundee.ac.uk

Hi.

Interesting question Mungo - and perhaps you may not have realised that
it doesn't have a clear cut answer.

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).

Threonine does have some hydrophobic characteristics - but these are
context dependent. The sidechain is relatively small, and dominated by
polar groups, so whilst it doesn't hydrogen bond terribly well with
water, its polarizable nature allows it to mix, so the entropic
solvation cost is not huge.

The original reference for this diagram is Taylor 1986 'The
classification of amino acid conservation', and many people have redrawn
it in subsequent publications. Most interpretations of physicochemical
properties at that time were based on empirical scales derived from
solubility measurements of the monomer, rather than any protein
environment based rational (although there were sufficient structures
available to support the hydrophobic core theory). As we get more
structures, we also get a better idea of amino acid spatial preferences.

Question remains, which is it (for Jalview conservation purposes at least)?

What is important for Jalview right now is that the method and reference
data used are those that is widely accepted (warts and all).

I think it would be posible to offer configuration to support different
forms of the matrix in a future release, but only experts will really
use that feature - and then, they may prefer to use entirely different
forms of physichemical conservation measurement. I've mentioned one key
resource for this before: http://www.genome.jp/aaindex/

For further reading I suggest you first take a look at Valdar 2002 :
valdarlab.unc.edu/papers/proteins2002.pdf

Jim.

···

On 02/11/2016 09:11, Mungo Carstairs (Staff) wrote:

--
-------------------------------------------------------------------
Dr JB Procter, Jalview Coordinator, The Barton Group
Division of Computational Biology, School of Life Sciences
University of Dundee, Dundee DD1 5EH, UK.
+44 1382 388734 | www.jalview.org | www.compbio.dundee.ac.uk

Thanks Jim!

…still waiting for a straight answer though…

☹

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
www.compbio.dundee.ac.uk

···

From: jalview-dev-bounces@jalview.org jalview-dev-bounces@jalview.org on behalf of James Procter j.procter@dundee.ac.uk
Sent: 02 November 2016 10:10:09
To: jalview-dev@jalview.org
Subject: Re: [Jalview-dev] Is Threonine hydrophobic?

Hi.

Interesting question Mungo - and perhaps you may not have realised that
it doesn’t have a clear cut answer.

On 02/11/2016 09:11, Mungo Carstairs (Staff) wrote:

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).

Threonine does have some hydrophobic characteristics - but these are
context dependent. The sidechain is relatively small, and dominated by
polar groups, so whilst it doesn’t hydrogen bond terribly well with
water, its polarizable nature allows it to mix, so the entropic
solvation cost is not huge.

The original reference for this diagram is Taylor 1986 ‘The
classification of amino acid conservation’, and many people have redrawn
it in subsequent publications. Most interpretations of physicochemical
properties at that time were based on empirical scales derived from
solubility measurements of the monomer, rather than any protein
environment based rational (although there were sufficient structures
available to support the hydrophobic core theory). As we get more
structures, we also get a better idea of amino acid spatial preferences.

Question remains, which is it (for Jalview conservation purposes at least)?

What is important for Jalview right now is that the method and reference
data used are those that is widely accepted (warts and all).

I think it would be posible to offer configuration to support different
forms of the matrix in a future release, but only experts will really
use that feature - and then, they may prefer to use entirely different
forms of physichemical conservation measurement. I’ve mentioned one key
resource for this before: http://www.genome.jp/aaindex/

For further reading I suggest you first take a look at Valdar 2002 :
valdarlab.unc.edu/papers/proteins2002.pdf

Jim.

Dr JB Procter, Jalview Coordinator, The Barton Group
Division of Computational Biology, School of Life Sciences
University of Dundee, Dundee DD1 5EH, UK.
+44 1382 388734 | www.jalview.org | www.compbio.dundee.ac.uk


Jalview-dev mailing list
Jalview-dev@jalview.org
http://www.compbio.dundee.ac.uk/mailman/listinfo/jalview-dev

The University of Dundee is a registered Scottish Charity, No: SC015096

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.

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
www.compbio.dundee.ac.uk


From: jalview-dev-bounces@jalview.org jalview-dev-bounces@jalview.org on behalf of Geoff Barton gjbarton@dundee.ac.uk
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.

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
www.compbio.dundee.ac.uk

The University of Dundee is a registered Scottish Charity, No: SC015096

_______________________________________________
Jalview-dev mailing list
[Jalview-dev@jalview.org](mailto:Jalview-dev@jalview.org)
[http://www.compbio.dundee.ac.uk/mailman/listinfo/jalview-dev](http://www.compbio.dundee.ac.uk/mailman/listinfo/jalview-dev)

The University of Dundee is a registered Scottish Charity, No: SC015096

The University of Dundee is a registered Scottish Charity, No: SC015096

···

On 02/11/2016 09:11, Mungo Carstairs (Staff) wrote:

On 01/11/2016 12:43, Mungo Carstairs (Staff) wrote:

-- 
Geoff Barton | Professor of Bioinformatics | Head of Division of Computational Biology   
School of Life Sciences | University of Dundee, Scotland, UK | [g.j.barton@dundee.ac.uk](mailto:g.j.barton@dundee.ac.uk) 
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 

-- 
Geoff Barton | Professor of Bioinformatics | Head of Division of Computational Biology   
School of Life Sciences | University of Dundee, Scotland, UK | [g.j.barton@dundee.ac.uk](mailto:g.j.barton@dundee.ac.uk) 
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 

Indeed. The Taylor Venn Diagram is not based on emprical scales of
"hydrophobicity" etc, but on observed substitution data. This captures
a lot more detail and subtlety from evolutionary constraints on protein
structure than biophysical measurements that only consider one property.

Geoff.

···

On 02/11/2016 10:10, James Procter wrote:

Hi.

Interesting question Mungo - and perhaps you may not have realised that
it doesn't have a clear cut answer.

On 02/11/2016 09:11, Mungo Carstairs (Staff) wrote:

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).

Threonine does have some hydrophobic characteristics - but these are
context dependent. The sidechain is relatively small, and dominated by
polar groups, so whilst it doesn't hydrogen bond terribly well with
water, its polarizable nature allows it to mix, so the entropic
solvation cost is not huge.

The original reference for this diagram is Taylor 1986 'The
classification of amino acid conservation', and many people have redrawn
it in subsequent publications. Most interpretations of physicochemical
properties at that time were based on empirical scales derived from
solubility measurements of the monomer, rather than any protein
environment based rational (although there were sufficient structures
available to support the hydrophobic core theory). As we get more
structures, we also get a better idea of amino acid spatial preferences.

Question remains, which is it (for Jalview conservation purposes at least)?

What is important for Jalview right now is that the method and reference
data used are those that is widely accepted (warts and all).

I think it would be posible to offer configuration to support different
forms of the matrix in a future release, but only experts will really
use that feature - and then, they may prefer to use entirely different
forms of physichemical conservation measurement. I've mentioned one key
resource for this before: AAindex: Amino acid index database

For further reading I suggest you first take a look at Valdar 2002 :
valdarlab.unc.edu/papers/proteins2002.pdf

Jim.

--
Geoff Barton | Professor of Bioinformatics | Head of Division of Computational Biology
School of Life Sciences | University of Dundee, Scotland, UK | g.j.barton@dundee.ac.uk
Tel: +44 1382 385860 | 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

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
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

-- 
Geoff Barton | Professor of Bioinformatics | Head of Division of Computational Biology   
School of Life Sciences | University of Dundee, Scotland, UK | [g.j.barton@dundee.ac.uk](mailto:g.j.barton@dundee.ac.uk) 
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

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
www.compbio.dundee.ac.uk


From: jalview-dev-bounces@jalview.org jalview-dev-bounces@jalview.org on behalf of Geoff Barton gjbarton@dundee.ac.uk
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

The University of Dundee is a registered Scottish Charity, No: SC015096

_______________________________________________
Jalview-dev mailing list
[Jalview-dev@jalview.org](mailto:Jalview-dev@jalview.org)
[http://www.compbio.dundee.ac.uk/mailman/listinfo/jalview-dev](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 | [g.j.barton@dundee.ac.uk](mailto:g.j.barton@dundee.ac.uk) 
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

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
www.compbio.dundee.ac.uk

Jumping in here before Geoff...

The bottom line seems to be that Jalview code treats Threonine as not
hydrophobic.

OK. So that's in agreement with 'most' googleable sources.

This is a bug if the intention is to match the diagram and matrix
published to support the method.

If anything, the bug is only that the matrix doesn't reflect what
Jalview uses. It would be good to also add some additional documentation
and links to appropriate reference sources too.

Jim is of the opinion that we should correct this, but keep the default
behaviour backwards compatible with past versions.

Contrary to what I said in our standup today, there is precedence for
simply changing the matrix in the code in line with the diagram. When I
was working on N-glycosylation patterns with Jalview, I noticed that N
was marked as charged in the matrix, but in the diagram it is simply
small and polar. I silently changed it.

Whether that was the 'right thing' 7 years ago is a good question.

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?

https://svn.lifesci.dundee.ac.uk/svn/barton/software/amas/
(log in with your Lifecci password)

A question on treatment of gaps:

(over to Geoff)

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.

I thought it was mentioned somewhere... odd that it never made it!
Easily fixed of course. As I've emailed in our private thread on this -
there are experts who would like to change these thresholds (e.g.
compute conservation over just the non-gapped sequences in each column,
and don't ignore residues with abundances less than a certain threshold).

Jim.

···

On 02/11/2016 11:38, Mungo Carstairs (Staff) wrote:

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Dr JB Procter, Jalview Coordinator, The Barton Group
Division of Computational Biology, School of Life Sciences
University of Dundee, Dundee DD1 5EH, UK.
+44 1382 388734 | www.jalview.org | www.compbio.dundee.ac.uk