Successful prediction of the coiled coil geometry of the GCN4 leucine zipper domain by simulated annealing: comparison to the X-ray structure.

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 A 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 chi 1, chi 2, chi 3, chi 4 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.