[Chimera-users] Hydrophobicity extensions

[Elaine Meng]

Hi Sam,
Although the menu preset is called "hydrophobicity surface," there is not really a thing called hydrophobicity surface. It is just a shorthand for showing the molecular surface, and then coloring it by hydrophobicity.  There is simply a lookup table for the hydrophobicity value of each amino acid residue, and the per-residue surface patches simply get colored by their residue's value.  There is no single value of overall surface hydrophobicity calculated for the protein; instead this preset is meant for visualization (not precise quantification) of the predominance of hydrophobicity at the surface and its spatial distribution, for example to estimate the membrane-embedded portion of a membrane protein, or to characterize the types of ligands that might bind a certain pocket.  Chimera does not give you a single value that summarizes the hydrophobicity of a protein or its surface.

Now addressing the errors: when you say "does not work" I'm guessing that the molecular surface calculation is failing.  Then, of course, you can't color the surface by anything because it's not there.

As mentioned above, I don't think it would that meaningful to calculate a single value per protein.  However, if the purpose  is to visualize which parts of a protein's surface may be more or less hydrophobic, then I suggest using our newer program ChimeraX instead.  It uses a different method of calculating molecular surfaces that is not subject to the numerical failures that occur in Chimera.

ChimeraX homepage, download link is on the left:
<https://www.rbvi.ucsf.edu/chimerax/index.html>

In ChimeraX, you can color the surface by molecular lipophilic potential, MLP (different than the amino-acid lookup table in Chimera) as shown here <https://www.rbvi.ucsf.edu/chimerax/features.html#mlp> or you could use the amino-acid lookup approach the same as in Chimera.

Example ChimeraX commands: open a porin structure, show surface, and color surface by MLP:

open 1pho
surf
mlp

... or use a ChimeraX script to do Chimera-style coloring by amino acid hydrophobicity lookup, with the same coloring as in Chimera:

open https://rbvi.ucsf.edu/chimerax/docs/user/kyte-doolittle_hydrophobicity.cxc

You can just show that URL in a browser to see the ChimeraX commands it contains.  It's just a plain text file.

I hope this all makes sense.  Good luck with your project!
Elaine
-----
Elaine C. Meng, Ph.D.                       
UCSF Chimera(X) team
Department of Pharmaceutical Chemistry
University of California, San Francisco

> On Feb 26, 2021, at 4:20 AM, Sam Hopgood <sam.t.hopgood at gmail.com> wrote:
> 
> Hello, 
> I'm currently studying at Imperial to complete my final year project for my MSci in Chemistry, but due to remote working I have to take on more of a computational project rather than something lab based and I'm not too experienced in the area and neither is my group. 
> 
> I have been told to use chimera to model the hydrophobic surface of proteins and determine a value for the surface hydrophobicity that can be later linked to data collected from HIC studies. I've been told to use chimera to model this but even basic visualisation of the hydrophobic surface does not work for proteins as large as rubisco. 
> 
> I know this is a big ask and an open ended question but are you aware of any extensions available to use to mitigate this issue? Or are you aware of any techniques I could use utilising the software to calculate an actual value for the surface hydrophobicity?
> 
> I hope you are all keeping safe and well, and thank you for any insight!
> Best, 
> Sam