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Command: mlp

mlp  atom-spec  [ method  fauchere | brasseur | type5 | dubost | buckingham [ nexp  n ]] [ maxDistance  D ] [ spacing  s ] [ map  true | false ] [ surfaces  surf-model ] [ color  true | false ]  palette-options 

The command mlp calculates molecular lipophilicity potential (MLP) maps for proteins. Nonprotein atoms are ignored. By default, the results are shown with coloring on the molecular surface ranging from dark cyan (most hydrophilic) to white to dark goldenrod (most lipophilic) .

See also: color, surface, per-model clipping, measurements, custom presets, Protein-Ligand Binding Sites tutorial, the ChimeraX MLP highlight, lipophilicity coloring comparisons

The calculation is based on pyMLP:

Molecular structures: Perception, autocorrelation descriptor and SAR studies. System of atomic contributions for the calculation of the n-octanol/water partition coefficients. Broto P, Moreau G, Vandycke C. Eur J Med Chem. 1984;19(1):71-78.

MLPP: A program for the calculation of molecular lipophilicity potential in proteins. Laguerre M, Saux M, Dubost JP, Carpy A. Pharm. Sci. 1997;3(5-6):217-22.

... except with atomic lipophilicity values taken from:

Prediction of Hydrophobic (Lipophilic) Properties of Small Organic Molecules Using Fragmental Methods:‚ÄČ An Analysis of ALOGP and CLOGP Methods. Ghose AK, Viswanadhan VN, Wendoloski JJ. J Phys Chem A. 1998; 102(21):3762-3772.

To allow MLP coloring without adding explicit hydrogens, values for any attached hydrogens were “collapsed” onto those for the corresponding heavy atoms (see details and comparisons to the original values from pyMLP). The resulting lookup table includes the standard amino acids plus MLE (selenomethionine), HYP (hydroxyproline), UNK (backbone-only, typically used in lower-resolution protein structures where the amino acid type could not be discerned), and the peptide-capping residues PCA (pyroglutamic acid), ACE (acetyl), NME (methylamine), and NH2. Other atoms are ignored.

The potential at each grid point is a sum over the atomic contributions. Positive potentials correspond to more lipophilic (more hydrophobic) areas, negative to less lipophilic (more hydrophilic) areas. Optimizations for speed, including a distance cutoff, have been added in ChimeraX.

The method specifies how the atomic values propagate through space, with factors based on the distance d from the atom (default fauchere):

The maxDistance D is a distance cutoff beyond which an atom's contribution is ignored (default 5.0 Å). Increasing the cutoff increases calculation time; the results may change only subtly or more noticeably depending on the method.

The spacing s of the map grid can be specified in the range 0.1–10.0 Å (default 1.0). Decreasing the spacing increases map size and calculation time.

With color true (default), a molecular surface is generated as needed for each protein chain that contains any of the specified atoms, colored by the MLP, and the surface patches for those atoms are displayed. Alternatively, one or more pre-existing molecular surfaces for the atoms (for example, a surface that encloses all protein chains collectively) can be specified with the surfaces option. A separate MLP map is computed for each surface, and its value ranges reported in the Log.

Defaults for the coloring palette-options are

palette lipophilicity range -20,20

Different choices of method and/or maxDistance can give very different values, and the range may need to be adjusted.

With color false, a single MLP map will be calculated based on the specified atoms (disregarding any nonprotein atoms), and no surface calculations or coloring will be performed. This is only useful in combination with map true.

With map true (default false), MLP maps will be opened as volume models. This allows saving the map to a file and/or subsequently coloring surfaces by the map values using color sample without having to recalculate the map on the fly. The following example colors a surface cap (#1.1.1, from clipping surface #1.1) by MLP map #2 with the same coloring parameters as used for the rest of the surface, except 30% transparent:

open 1g74
mlp map true
hide #2
wait 1
color sample #1.1.1 map #2 palette lipophilicity range -20,20 transparency 30
clip model #!1 off
hide ~ligand targ ar

The wait command is only needed in the context of a script (command file), to force drawing the graphics to create the surface cap before it is colored by the map values. The wait can be omitted if the commands are entered one by one. The subsequent commands color the cap, make clipping apply only to the surface (not to the atomic model), and hide ribbons and atoms not classified as ligand.

UCSF Resource for Biocomputing, Visualization, and Informatics / July 2020