Conformational Parameters for Amino Acids in Helical, β-Sheet, and Random Coil Regions Calculated from Proteins: After 40 Years

Abstract

Forty years ago, Peter Y. Chou and Gerald D. Fasman (1974a), relying on the information from fifteen proteins calculated α helix, β-sheet, and coil conformational parameters, Pα,Pβ,and Pc,for the 20 naturally occurring amino acids from the frequency of occurrence of each amino acid residue in the α, β, and coil conformations. Secondary structure of these 15 proteins had been determined by X-ray crystallography. Although the accuracy could not go over to the level of 60% too much, these values utilized for a long time to provide a simple procedure, devoid of complex computer calculations, to predict the secondary structure of proteins from their known amino acid sequences. In the same article of Peter Y. Chou and Gerald D. Fasman, a detailed analysis of the helix and β-sheet boundary residues in proteins provided amino acid frequencies at the N-and C-terminal ends which were used to delineate helical and β regions. Charged residues are found with the greatest frequency at both helical ends, but they were mostly absent in β-sheet regions. In the same article a mechanism of protein folding was proposed, whereby helix nucleation starts at the centers of the helix where the Pα values are highest, and propagates in both directions, until strong helix breakers where Pα values are lowest, terminate the growth at both ends. Similarly, residues with the highest Pβ values will initiate β regions and residues with the lowest Pβ values will terminate β regions. The helical region with the largest Pα was proposed as the site of the first fold during protein renaturation. The mechanism whereby proteins fold into their native conformation, capable of biological activity, has been a long sought after goal. With the elucidation of the three-dimensional structure of many proteins through X-ray crystallography, a new momentum has been given to understanding the factors governing this complex assembly of polypeptide chains. In this paper, using similar statistics from 20 347 proteins, the level of reliability of formerly found results is discussed.