An algorithm for the detection of surface-active alpha helices with the potential to anchor proteins at the membrane interface.

Abstract

Motivation: Surface-active peptides are amphiphilic in nature and have been shown to have the potential to interact at the membrane interface, possibly by lying parallel to the membrane surface. Present methodology for the identification of these helices uses a fixed window size, is based on a two-dimensional sum of hydrophobicity vectors and gives no measure of the statistical significance for any region identified as amphiphilic. Identification of weakly surface-active structures is difficult and here we have attempted to remedy this by introducing an algorithm which considers three-dimensional geometries and variable window size.

Results: A new measure of membrane-interactive potential is proposed, called the depth-weighted inserted hydrophobicity (DWIH), which is based on the sequestration of hydrophobic residues within a hydrophobic compartment, such as that produced by a membrane bilayer. A statistical significance for this measure has been derived using Monte Carlo techniques. The algorithm is applied to a set of proteins which are thought to anchor to the membrane via C-terminal amphiphilic alpha helices. The DWIH measure appears to allow the identification of this category of membrane-interactive helices which lie near the boundary of the hydrophobic moment plot and which have previously been hard to classify.