| a-Helical integral-membrane proteins (IMPs) play a key role in many biological
processes, such as signal transduction, and are targets for >50% of
current therapeutic drugs. In contrast to their significant abundance and
biological importance, they comprise <1% of structurally solved proteins.
In the absence of experimental evidence, molecular modeling of IMP structures
is an alternative for providing structural information and aiding
further experimental design. In the current work, we propose two new
amino acid lipid-facing propensity scales derived from the structural analysis
of a nonredundant set of water-soluble proteins. The new scales, p and
d, perform as well or better than published scales (Carugo’s hydrophobicity
and kPROT scales) in predicting the lipid-facing side of helical segments of
a set of structurally solved IMPs, thus indicating (a) that the folding properties
of water-soluble proteins and IMPs are similar, and (b) that the new
scales will prove useful in modeling the transmembrane segments of IMPs. |