Monte Carlo simulation studies on the prediction of protein folding types from amino acid composition

Abstract

A number of methods to predicting the folding type of a protein based on its amino acid composition have been developed during the past few years. In order to perform an objective and fair comparison of different prediction methods, a Monte Carlo simulation method was proposed to calculate the asymptotic limit of the prediction accuracy [Zhang and Chou (1992),Biophys. J. 63, 1523–1529, referred to as simulation method I]. However, simulation method I was based on an oversimplified assumption, i.e., there are no correlations between the compositions of different amino acids. By taking into account such correlations, a new method, referred to as simulation method II, has been proposed to recalculate the objective accuracy of prediction for the least Euclidean distance method [Nakashimaet al. (1986),J. Biochem. 99, 152–162] and the least Minkowski distance method [Chou (1989),Prediction in Protein Structure and the Principles of Protein Conformation, Plenum Press, New York, pp. 549–586], respectively. The results show that the prediction accuracy of the former is still better than that of the latter, as found by simulation method I; however, after incorporating the correlative effect, the objective prediction accuracies become lower for both methods. The reason for this phenomenon is discussed in detail. The simulation method and the idea developed in this paper can be applied to examine any other statistical prediction method, including the computersimulated neural network method.