PREDICTION OF PROTEIN SECONDARY STRUCTURE FROM CIRCULAR-DICHROISM SPECTRA - AN ATTEMPT TO SOLVE THE PROBLEM OF THE BEST-FITTING REFERENCE PROTEIN SUBSETS

In least-squares fitting of protein circular dichroism (CD) spectra us ing basis CD spectra for the respective secondary structure components , as given by reference proteins of known structural composition, good fits of the CD spectrum do not necessarily correspond to appropriate fits of the underlying structural composition of a test protein, In an attempt to overcome this problem, CD similarity measures were used to construct a subset of five reference CD spectra which permitted three -component fitting of the CD and prediction of the relative magnitude of total beta-sheet (antiparallel + parallel) and total other structur e (beta-turn + remainder), relative to helix, in the test protein. A b ackpropagation neural network (BPN) was also trained to make this pred iction, In subsequent five-component fitting of the CD spectrum, using a Monte Carlo method to generate subsets of reference proteins from t he working data set, only those secondary structure fits which conform ed to the consensus prediction of the CD similarity measures and the B PN were accepted, The method enhanced the fitting of antiparallel beta -sheet and beta-turn for 16 proteins, compared to the variable selecti on method of P, Manavalan and W. C, Johnson (1987, Anal, Biochem, 167, 76-85), Some other proteins were less well fitted. Improvement in res ults is expected with a larger representation of feasible basis CD spe ctra in the working reference proteins, (C) 1995 Academic Press,Inc.