[Chimera-users] surface hydrophobicity display

[Miguel Ortiz Lombardia]

Le 31/01/2011 20:16, Elaine Meng a écrit :
> In that paper, they only looked at Coulombic ESP (and its gradient), but one might expect as least as good results with a more sophisticated ESP.  However, you  (Sumitro) already said that you were using Coulombic rather than the other methods to calculate electrostatic potential.
> 
> You can use the "Compute grid" option of Coulombic Surface Coloring to create a grid file, and then do the gradient coloring that Tom describes with the Surface Color tool.
> <http://www.cgl.ucsf.edu/chimera/docs/ContributedSoftware/coulombic/coulombic.html>
> <http://www.cgl.ucsf.edu/chimera/docs/ContributedSoftware/surfcolor/surfcolor.html>
> 
> However, that still leaves open the question of whether any ESP gradient is an adequate measure of hydrophobicity.
> 
> That J Med Chem 1992 paper is frustrating because it has several graphs where the lines all look the same, so it is hard to tell what is what.  Maybe it exists somewhere in color, where you can tell the lines apart, but I only found black and white.
> Elaine
> 
> On Jan 31, 2011, at 11:02 AM, Tom Goddard wrote:
> 
>> Hi Elaine,
>>
>>  Occurs to me that if the electric field strength, ie the gradient of the electrostatic potential, is a useful measure similar to hydrophobicity, that can be viewed currently in Chimera with the surface color dialog using color by "volume data gradient norm".  You would need the electrostatic potential calculated for instance by APBS or DelPhi.
>>
>>    Tom
>>
>>> Hi Sumitro,
>>> I did a little more digging for related information and thought I would share -- however, none of these methods are available in Chimera currently.
>>>
>>> ...  If I understood it correctly, they looked at how successfully Coulombic electrostatic potential and the gradient in that potential can be used to identify hydrophobic areas of surface (areas that bind hydrophobic atoms in the ligand).  Both were somewhat successful, but even better was a simple definition of hydrophobic surface as the part of the surface that is not close to hydrogen-bonding groups.  This paper is fairly old and the data set of ligand/receptor structures small.
>>>
>>>
>>> Elaine
>>

Thank you Elaine and Tom for this interesting discussion. Sorry for my
misunderstanding of Elaine's first answer to Sumitro.

The work I mentioned (by Goodford) uses a different approach that is not
related (at least not directly as far as I can understand it) with the
electrostatic potential. They use a "dry" (originally a methane, I
think), hydrophobic probe that is rolled over the protein surface and
the energy of interaction of this probe with the protein is calculated
at every point of a certain grid. From the three main components of the
GRID force field only the Lennard-Jones seems relevant here (the other
two are electrostatic - but the "dry" probe is neutral - and hydrogen
bond potential)

I am not sure the results would be the same as looking at the
electrostatic potential, as Tom suggests, and I cannot check it,
obviously. Thank you, Elaine, for these references! The notion of
hydrophobicity as a measure of distance to hydrogen-bonding atoms seems
also interesting (and looks as easier to implement than the GRID approach)


Best regards,


-- 
Miguel

Architecture et Fonction des Macromolécules Biologiques (UMR6098)
CNRS, Universités d'Aix-Marseille I & II
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http://www.afmb.univ-mrs.fr/Miguel-Ortiz-Lombardia

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