Prediction of Protein Conformation

Abstract

A new predictive model for the secondary structure of globular proteins (α helix, β sheet, and β turns) is described utilizing the helix and β-sheet conformational parameters, Pα and Pβ, of the 20 amino acids computed in the preceding paper (Chou and Fasman, 1974). This simple and direct method, devoid of complex computer calculations, utilizes empirical rules for predicting the initiation and termination of helical and β regions in proteins. Briefly stated: when four helix formers out of six residues or three β formers out of five residues are found clustered together in any native protein segment, the nucleation of these secondary structures begins and propagates in both directions until terminated by a sequence of tetrapeptides, designated as breakers. These rules were successful in locating 88% of helical and 95 % of β regions, as well as correctly predicting 80% of the helical and 86% of the β-sheet residues in the 19 proteins evaluated. The accuracy of predicting the three conformational states for all residues, helix, β, and coil, is 77% and shows great improvement over earlier prediction methods which considered only the helix and coil states. The β-turn conformational parameters, Pt, for all 20 amino acids are computed. Their use enables the prediction of chain reversal and tertiary folding in proteins. A procedure for predicting conformational changes in specific regions is also outlined. Despite some evidence of long-range interactions in stabilizing protein folding, the present predictive model illustrates that short-range interactions (i.e., single residue information as represented by Pα and Pβ) and medium-range interactions (i.e., neighboring residue information as represented by (Pα) and (Pβ) play the predominant role in determining protein secondary structure. Although the three-dimensional structures of only 19 proteins have been elucidated to date via X-ray studies, the amino acid sequences of hundreds of proteins have already been determined. Since the present predictive model is capable of delineating the helix, β, and coil regions of proteins of known sequence with 80% accuracy, application of this method will be of assistance to all those interested in studying the correlation between protein conformation and biological activity as well as an aid to crystallographers in interpreting X-ray data. © 1974, American Chemical Society. All rights reserved.