Abstract
With the advent of molecular cloning methods, the amino acid sequences for a number of membrane proteins have been determined. The relative paucity of detailed three-dimensional structural information available for these molecules has led to attempts to predict the secondary structures of membrane proteins based on folding motifs found in soluble proteins of known three-dimensional structure and sequence. In this study, we evaluated the accuracy of several of these methods in predicting the conformation of 15 integral membrane proteins and membrane-spanning polypeptides for which both primary and secondary structural information are available. chi 2 analyses indicated a less than 0.5% correlation between the net predicted secondary structures and the experimental results. A more stringent test of the accuracy of the methods, the index of prediction, was calculated for individual residues in four of the polypeptides for which the crystal structures were known; this criterion also indicated that the predicted assignments for the secondary structures of the residues were inaccurate. Thus, prediction schemes using soluble protein bases appear to be inappropriate for the prediction of membrane protein folding.