Prediction of transmembrane helices from hydrophobic characteristics of proteins.

Membrane proteins, requiring to be embedded into the lipid bilayers, have evolved to have amino acid sequences that will fold with a hydrophobic surface in contact with the alkane chains of the lipids and polar surface in contact with the aqueous phases on both sides of the membrane and the polar head groups of the lipids. It is generally assumed that the characteristics of the aqueous parts of the membrane proteins are similar to those of normal globular proteins, and the embedded parts are highly hydrophobic. In our earlier works, we introduced the concept of 'surrounding hydrophobicity' and developed a hydrophobicity scale for the 20 amino acid residues, and applied it successfully to the study of the family of globular proteins. In this work we use the concept of surrounding hydrophobicity to indicate quantitatively how the aqueous parts of membrane proteins compare with the normal globular proteins, and how rich the embedded parts are in their hydrophobic activity. We then develop a surrounding hydrophobicity scale applicable to membrane proteins, by mixing judicially the surrounding hydrophobicities observed in the crystals of the membrane protein, photosynthetic reaction center from the bacterium Rhodopseudomonas viridis, porin from Rhodobacter capsulatus and a set of 64 globular proteins. A predictive scheme based on this scale predicts from amino acid sequence, transmembrane segments in PRC and randomly selected 26 membrane proteins to 80% level of accuracy. This is a much higher predictive power when compared to the existing popular methods. A new procedure to measure the amphipathicity of sequence segments is proposed, and it is used to characterize the transmembrane parts of the sample membrane proteins.