Molecular Lipophilicity Potential

Elaine Meng
Aug-Sep 2016

MLP (or MHP for molecular hydrophobicity potential) is a construct that spreads atomic values out in 3D, analogous to an electrostatic potential calculated from atomic partial charges. It is not clearly defined, so various different functional forms are used, as well as different sets of atomic parameters. Most of the emphasis in papers about the atomic contributions is on using them to predict the logP (octanol-water partition coefficient) of entire small organic molecules. Coloring/display of “hydrophobicity potential” is a later application.

Qualitative conclusion from the limited set of comparisons below: for protein depiction, a simple amino acid lookup may be be better than or at least as good as than a potential, given the latter's complexity, computational demands, and dependence on reasonable atomic values. See for example the result of simply averaging PLATINUM atomic values over residues without using a distance-dependent equation (below). The atomic values used by pyMLP and thus mlp in ChimeraX may not be that good; however, for the comparisons here I did not explore the different functional forms and other adjustable parameters in mlp (details...). The possible advantage of an atom-type-based potential is that it could be used on arbitrary organic compounds, but this has not been implemented in ChimeraX yet. Ideally we'd have both:

Aug 17, 2016. Trying the PLATINUM server http://model.nmr.ru/platinum/ on membrane protein rhodopsin, 1hzx chain A:

input atomic values,
range -1.76, 0.76
("bfactor" in 1hzxAwithH_atomic.pdb)
input atomic values but residue avg,
range -0.17, 0.11
(Chimera calc residue avg "bfactor")
output MHP at centers,
range -1, 1
("bfactor" in 1hzxAwithH_centers.pdb)
output MHP at surface,
range -1.5, 1.83
same thing but
coloring -1,0,1
(all others min,0,max)

... compare to current Chimera and ChimeraX options:

ChimeraX mlp
default parms
except color
min,0,max
min -45, max 25
ChimeraX mlp
same except color -20,0,20
(default coloring range)
ChimeraX mlp
default everything
Chimera
kdHydrophobicity
color min,0,max
Chimera
wwHydrophobicity
color min,0,max
Chimera
wwHydrophobicity
color -1,0,1
Chimera
hhHydrophobicity
color min,0,max
*negative is more hydrophobic in this scale*
Chimera
mfHydrophobicity
(sugg by Oliver,
see below)
color min,0,max
*negative is more hydrophobic in this scale*
**I did not explore the different functional forms and other adjustable parameters in ChimeraX mlp (details...), which might have given results more like the other methods.** With mlp defaults, a more impressive case is 1a0s (sucrose-specific porin).

Files for/from the PLATINUM server (more details in their manual):

From the PLATINUM manual:
MHP table: ...make sure that hydrogen atoms were added prior uploading files... The major changes in the new table relate more realistic negative (hydrophilic) constants for some heteroatom types, particularly oxygen...

Distance function:

...Since MHP is an empirical approach, no “exact” distance-dependent decay function is known...
They further recommend adding a constant offset of 0.03 to each atomic value before the calculation.

The Ghose paper lists atomic MHP values by atom type, not PDB atom/res name. Thus it would probably take some work to use this in ChimeraX, similar to VDW radius assignment in Chimera: identifying the atom types and then mapping them to the values.

Related suggestion from Oliver Clarke, July 2016: http://plato.cgl.ucsf.edu/pipermail/chimera-users/2016-July/012562.html