Efficient determination of protein crystal structures requires automated x-ray data analysis. Here, we describe the expert system ELVES and its use to determine automatically the structure of a 12-kDa protein. Multiwavelength anomalous diffraction analysis of a selenomethionyl derivative was used to image the Asn-16-Ala variant of the GCN4 leucine zipper. In contrast to the parallel, dimeric coiled coil formed by the WT sequence, the mutant unexpectedly formed an antiparallel trimer. This structural switch reveals how avoidance of core cavities at a single site can select the native fold of a protein. All structure calculations, including indexing, data processing, locating heavy atoms, phasing by multiwavelength anomalous diffraction, model building, and refinement, were completed without human intervention. The results demonstrate the feasibility of automated methods for determining high-resolution, x-ray crystal structures of proteins.