Successful prediction of the coiled coil geometry of the GCN4 leucine zipper domain by simulated annealing: Comparison to the X‐ray structure

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Abstract
The recently solved X‐ray structure of the dimerization region (“leucine zipper”) of the yeast transcriptional activator GCN4 (O'Shea, E. K., Klemm, J. D., Kim, P. S., Alber, T. Science 254:539–544, 1991) is compared to previously predicted models which had been obtained by a conformational search procedure employing simulated annealing without any knowledge of the crystal coordinates (Nilges, M., Brünger, A. T. Protein Eng. 4:649–659,1991). During the course of the simulated annealing procedure, the models converged towards the X‐ray structure. The averaged root mean square difference between the models and the X‐ray structure is 1.26 and 1.75 Å for backbone atoms and all nonhydrogen atoms at the dimerization interface, respectively. The local helix–helix crossing angle of the X‐ray structure falls within the range predicted by the models; a slight unwinding of the coiled coil toward the N‐terminal DNA‐binding end of the dimerization region has been correctly predicted. Distance maps between the helices are largely identical. The region around asparagine 20 is asymmetric in the X‐structure and in the models. Surface side chain dihedrals showed a large variation in the models although the χ1, χ2, χ3, χ4 3‐fold dihedrals were correctly predicted in 69, 42, 43, and 44% of the cases, respectively. Phenomenological free energies of dimerization of the models show little correlation with the root mean square difference between the models and the X‐ray structure.