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 Case 932, 163 Avenue de Luminy, 13288 Marseille cedex 9, France Tel: +33(0) 491 82 55 93 Fax: +33(0) 491 26 67 20 mailto:miguel.ortiz-lombardia@afmb.univ-mrs.fr http://www.afmb.univ-mrs.fr/Miguel-Ortiz-Lombardia -- This message has been scanned for viruses and dangerous content by MailScanner, and is believed to be clean.