Hydrophobicity scales: Prediction of residue location and trans-membrane regions

A "hydrophobicity value" can be assigned to each of the 20 amino acids. These give a measure of the partition between water (polar) and hydrophobic (non-polar) environments.

There are many hydrophobicity scales derived using different methods including: free energy of transfer between polar and non-polar solvents, observed solvent accessibilities or buriedness, hydration on freezing, chromatographic mobility in apolar solvent, HPLC retention times and effect on surface tension of water. Consensus scales have also been created (e.g. Kyte & Doolittle, J. Mol. Biol. 157(1982)105-132; Eisenberg et al., Faraday Symp. Chem. Soc. 17(1982)109)

See Cornette et al. J. Mol. Biol 195(1987)659-685 for a comparison of 38 published scales.

Hydrophobicity plots have been used to locate membrane-spanning segments and exposed vs., buried portions of soluble globular proteins

Trans-membrane (TM) proteins are of great biological importance: One third of the top 100 pharamceuticals bind to TMs (e.g. Voltage-gated channels, NMDA receptors, g-protein coupled receptors (GPCRs)).

Experimental structure determination of TM proteins is difficult.

Prediction of TM regions is relatively easy as:

• they are strongly hydrophobic and ~25 amino acids long
• the cytoplasmic side is largely positively charged