10.1. Determining the Structures of Proteins

If we can experimentally determine the structures of proteins, and structure prediction is so hard, why bother with predicting structure at all? The answer is that solving protein structures is difficult, and there are many bottlenecks in the experimental process. Although the first protein structure was determined decades before the first DNA sequence, the protein structure database has grown far more slowly in the interim than the sequence database. There are now on the order of 10,000 protein structures in the PDB, and on the order of 10 million gene sequences in GenBank. Only about 3,000 unique protein structures have been solved (excluding structures of proteins that are more than 95% identical in sequence). Approximately 1,000 of these are from proteins that are substantially different from each other (no more than 25% identical in sequence).

10.1.1. Solving Protein Structures by X-ray Crystallography

In the late 1930s, it was already known that proteins were made up of amino acids, although it had not yet been proven that these components came together in a unique sequence. Linus Pauling and Robert Corey began to use x-ray crystallography to study the atomic structures of amino acids and peptides.