PREDICTION OF THE 3-DIMENSIONAL STRUCTURE OF PROTEINS USING THE ELECTROSTATIC SCREENING MODEL AND HIERARCHICAL CONDENSATION

We describe a method for predicting the three-dimensional (3-D) struct ure of proteins from their sequence alone. The method is based on the electrostatic screening model for the stability of the protein main-ch ain conformation. The free energy of a protein as a function of its co nformation is obtained from the potentials of mean force analysis of h igh-resolution x-ray protein structures, The free energy function is s imple and contains only 44 fitted coefficients. The minimization of th e free energy is performed by the torsion space Monte Carlo procedure using the concept of hierarchic condensation. The Monte Carlo minimiza tion procedure is applied to predict the secondary, super-secondary, a nd native 3-D structures of 12 proteins with 28-110 amino acids. The 3 -D structures of the majority of local secondary and super-secondary s tructures are predicted accurately. This result suggests that control in forming the native-like local structure is distributed along the en tire protein sequence, The native 3-D structure is predicted correctly for 3 of 12 proteins composed mainly from the alpha-helices. The meth od fails to predict the native 3-D structure of proteins with a predom inantly beta secondary structure. We suggest that the hierarchic conde nsation is not an appropriate procedure for simulating the folding of proteins made up primarily from beta-strands. The method has been prov ed accurate in predicting the local secondary and super-secondary stru ctures in the blind ab initio 3-D prediction experiment. (C) 1998 Wile y-Liss, Inc.