Hydrophobicity Scales
Hydrophobicity scales, composed of experimentally determined transfer free energies for each amino acid, are essential for understanding the energetics of protein-bilayer interactions. Two scales are needed, one for the transfer of unfolded chains from water to bilayer interface and one for the transfer of folded chains into the hydrocarbon interior.
That is, the scales must be whole-residue scales.
|
Amino Acid
|
Interface Scale
DGwif (kcal/mol)
|
Octanol Scale
DGwoct (kcal/mol)
|
Octanol - Interface Scale
|
|
Ala
|
0.17 +- 0.06
|
0.50 +- 0.12
|
0.33 +- 0.12
|
|
Arg+
|
0.81 +- 0.11
|
1.81 +- 0.13
|
1.00 +- 0.17
|
|
Asn
|
0.42 +- 0.06
|
0.85 +- 0.12
|
0.43 +- 0.13
|
|
Asp-
|
1.23 +- 0.07
|
3.64 +- 0.17
|
2.41 +- 0.18
|
|
Asp0
|
-0.07 +- 0.11
|
0.43 +- 0.13
|
0.50 +- 0.17
|
|
Cys
|
-0.24 +- 0.06
|
-0.02 +- 0.13
|
0.22 +- 0.14
|
|
Gln
|
0.58 +- 0.08
|
0.77 +- 0.12
|
0.19 +- 0.14
|
|
Glu-
|
2.02 +- 0.11
|
3.63 +- 0.18
|
1.61 +- 0.21
|
|
Glu0
|
-0.01 +- 0.15
|
0.11 +- 0.12
|
0.12 +- 0.19
|
|
Gly
|
0.01 +- 0.05
|
1.15 +- 0.11
|
1.14 +- 0.12
|
|
His+
|
0.96 +- 0.12
|
2.33 +- 0.11
|
1.37 +- 0.16
|
|
His0
|
0.17 +- 0.06
|
0.11 +- 0.11
|
-0.06 +- 0.13
|
|
Ile
|
-0.31 +- 0.06
|
-1.12 +- 0.11
|
-0.81 +- 0.13
|
|
Leu
|
-0.56 +- 0.04
|
-1.25 +- 0.11
|
-0.69 +- 0.12
|
|
Lys+
|
0.99 +- 0.11
|
2.80 +- 0.11
|
1.81 +- 0.16
|
|
Met
|
-0.23 +- 0.06
|
-0.67 +- 0.11
|
-0.44 +- 0.13
|
|
Phe
|
-1.13 +- 0.05
|
-1.71 +- 0.11
|
-0.58 +- 0.12
|
|
Pro
|
0.45 +- 0.12
|
0.14 +- 0.11
|
-0.31 +- 0.16
|
|
Ser
|
0.13 +- 0.08
|
0.46 +- 0.11
|
0.33 +- 0.14
|
|
Thr
|
0.14 +- 0.06
|
0.25 +- 0.11
|
0.11 +- 0.13
|
|
Trp
|
-1.85 +- 0.06
|
-2.09 +- 0.11
|
-0.24 +- 0.13
|
|
Tyr
|
-0.94 +- 0.06
|
-0.71 +- 0.11
|
0.23 +- 0.13
|
|
Val
|
0.07 +- 0.05
|
-0.46 +- 0.11
|
-0.53 +- 0.12
|
|
The idea that the octanol scale is useful for identifying TM segments. Because TM segments should generally prefer the bilayer rather than water, one would also expect the whole-residue interfacial scale to identify TM segments. In addition, however, one would expect true TM segments to have more favorable free energies on the octanol scale than on the interfacial scale. The hydropathy plot constructed using DGwoct- DGwif shows favorable peaks on the absolute scale that correspond to the known TM helices. Significantly, the maxima have more restricted sequence-ranges than seen with either of the scales alone and thus identify with less ambiguity the positions of the TM helices. These results make perfect sense: TM helices will choose to be associated with the membrane rather than the water and will prefer a TM location rather than a surface one. Were this not true, MPs would not be stably buried in the membrane.