Hydrophobicity Scales

CHAP associates each amino acid residue in a channel structure with a hydrophobicity value and uses this information to calculate a continuous hydrophobicity profile for the channel’s permeation pathway as well as to produce hydrophobicity-coloured pore visualisations. In order to do this, it relies on published amino acid hydrophobicity scales. This page is intended to document the available hydrophobicity scales and to describe how custom scales can be added by a user.

Hydrophobicity Scales in CHAP

The hydrophobicity scale data used by CHAP can be found in the chap/share/data/hydrophobicity/ directory, with each scale contained in an individual JSON file. Each file contains not only the scale data itself, but also a reference to the publication from which the data was taken. For convenience, these references are repeated in the table below:

Scale Name Reference DOI or Weblink
hessa_2005 Hessa, Tara, et al. “Recognition of transmembrane helices by the endoplasmic reticulum translocon.” Nature 433.7024 (2005): 377-381. 10.1038/nature03216
kyte_doolittle_1982 Kyte, Jack, and Russell F. Doolittle. “A simple method for displaying the hydropathic character of a protein.” Journal of molecular biology 157.1 (1982): 105-132. 10.1016/0022-2836(82)90515-0
memprotmd Newport, Thomas D. et al. “MemProtMD: A Database of Membrane Proteins Embedded in Lipid Bilayers” www.memprotmd.bioch.oc.ac.uk/stats
monera_1995 Monera, Oscar D., et al. “Relationship of sidechain hydrophobicity and α‐helical propensity on the stability of the single‐stranded amphipathic α‐helix.” Journal of peptide science 1.5 (1995): 319-329. 10.1002/psc.310010507
moon_2015 Moon, C. Preston, and Karen G. Fleming. “Side-chain hydrophobicity scale derived from transmembrane protein folding into lipid bilayers.” Proceedings of the National Academy of Sciences 108.25 (2011): 10174-10177. 10.1073/pnas.1103979108
wimley_white_1996 Wimley, William C., and Stephen H. White. “Experimentally determined hydrophobicity scale for proteins at membrane interfaces.” Nature Structural & Molecular Biology 3.10 (1996): 842-848. 10.1038/nsb1096-842
zhu_2016 Zhu, Chongqin, et al. “Characterizing hydrophobicity of amino acid side chains in a protein environment via measuring contact angle of a water nanodroplet on planar peptide network.” Proceedings of the National Academy of Sciences (2016): 201616138. 10.1073/pnas.1616138113

In order to make the different scales comparable, hydrophobicity values have been linearly scaled to the interval [-1,1], with +1 being the most hydrophobic, -1 the most hydrophilic, and 0 a neutral residue. Where hydrophobicities have been scaled, the JSON file will also contain the originally published values in the original_hydrophobicity record.

Users can control which hydrophobicity scale is applied by setting the -hydrophob-database flag. By default, the wimley_white_1996 scale is used. Note that all available scales only provide hydrophobicity data for amino acid residues. If the pathway-forming group (specified with the -sel-pathway flag) contains any other residues, you either have to provide a fallback hydrophobicity value with the -hydrophob-fallback flag or provide a custom hydrophobicity scale as described in the following section.

Adding Custom Hydrophobicity Scales

In order to provide a custom hydrophobicity scale to CHAP, the -hydrophob-database flag needs to be set to user and the -hydrophob-json flag needs to point to a JSON file containing the scale data.

The easiest way to create a hydrophobicity scale JSON file will be to adapt one of the existing files in chap/share/data/hydrophobicity/. Note that the only required record in this file is an object named hydrophobicity that contains an array of residue name and hydrophobicity value pairs as in the example below:

    "hydrophobicity": [
        {"resname": "ALA", "hydrophobicity": -0.13692946},
        {"resname": "ARG", "hydrophobicity": -0.41493776},
        {"resname": "ASN", "hydrophobicity": -0.17842324},
        {"resname": "ASP", "hydrophobicity": -1.00000000},
        {"resname": "CYS", "hydrophobicity": -0.09128631},
        {"resname": "GLN", "hydrophobicity": -0.07883817},
        {"resname": "GLU", "hydrophobicity": -0.66804979},
        {"resname": "GLY", "hydrophobicity": -0.47302905},
        {"resname": "HIS", "hydrophobicity": -0.56846473},
        {"resname": "ILE", "hydrophobicity":  0.33609959},
        {"resname": "LEU", "hydrophobicity":  0.33609959},
        {"resname": "LYS", "hydrophobicity": -0.75103734},
        {"resname": "MET", "hydrophobicity":  0.18257261},
        {"resname": "PHE", "hydrophobicity":  0.24066390},
        {"resname": "PRO", "hydrophobicity":  0.12863071},
        {"resname": "SER", "hydrophobicity": -0.13692946},
        {"resname": "THR", "hydrophobicity": -0.04564315},
        {"resname": "TRP", "hydrophobicity":  0.09958506},
        {"resname": "TYR", "hydrophobicity": -0.09543568},
        {"resname": "VAL", "hydrophobicity":  0.21991701}

For consistency, you should rescale your hydrophobicity values to the interval [-1, 1] as described in the foregoing section.

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