[Chimera-users] surface hydrophobicity display

[Elaine Meng]

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.

Miguel Ortiz Lombardia has pointed out that the GRID program calculates a hydrophobic potential, and sent us the following links:
<http://biop.ox.ac.uk/www/lj2000/noble/noble_02.html>
<http://www.moldiscovery.com/docs/vsplus/grid.html>

-- the following web server sounded promising, but apparently no longer exists:

PLATINUM: a web tool for analysis of hydrophobic/hydrophilic organization of biomolecular complexes.
Pyrkov TV, Chugunov AO, Krylov NA, Nolde DE, Efremov RG.
Bioinformatics. 2009 May 1;25(9):1201-2.
<http://www.ncbi.nlm.nih.gov/pubmed/19244385>

-- the following paper discusses what surface properties of the receptor correlate well with the types of nearby ligand atoms.  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.

Definition and display of steric, hydrophobic, and hydrogen-bonding properties of ligand binding sites in proteins using Lee and Richards accessible surface: validation of a high-resolution graphical tool for drug design.
Bohacek RS, McMartin C.
J Med Chem. 1992 May 15;35(10):1671-84.
<http://www.ncbi.nlm.nih.gov/pubmed/1588550>

-- then there are some other complicated functions based on molecular fragments and distances among them and to the molecular surface:
A new approach to analysis and display of local lipophilicity/hydrophilicity mapped on molecular surfaces.
Heiden W, Moeckel G, Brickmann J.
J Comput Aided Mol Des. 1993 Oct;7(5):503-14.

Estimating and representing hydrophobicity potential
Fauchere et al.
Journal of Molecular Graphics
Volume 6, Issue 4, December 1988, Pages 203-206

If I understood correctly, these have many parameters and the functional form is not simple.  It  would not be straightforward to put them into Chimera.  Finally, I also saw that the program MDL Chime has something called hydrophobic potential display, but I couldn't find a description of how it really works  -- it might just be coloring whole amino acids by hydrophobicity value like Chimera does now, or atoms based on element.

Elaine
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Elaine C. Meng, Ph.D. 
UCSF Computer Graphics Lab (Chimera team) and Babbitt Lab
Department of Pharmaceutical Chemistry
University of California, San Francisco