language applies to humans, plants, and microbes. This universality makes genetic engineering and gene therapy feasible.

Recent advances in technology, using modern chemical techniques for structure determination, have allowed us to sequence or read the letters in the DNA, or genome, of a cell. We have genomic sequence data for humans, an insect, a plant, simple multicellular organisms, and many microbes; more are constantly being produced. These sequences represent the total genetic and biochemical blueprint for each of these organisms. This information is useless unless we learn to read it intelligently; that is, to relate linear sequence information to cell and organismal function. Functional genomics is a term used to describe that relationship, and it will be a primary challenge for the next 50 years.

The simple sequence of letters in the genome tells us only a little. The details of three-dimensional structure are important to understanding the chemical processes of life. For example, the discovery that DNA forms a double helix made it clear how genetic information is passed on and utilized. The biological activity of the proteins encoded on the DNA is dependent on their specific three-dimensional structure. Many chemists are concerned with how best to determine the structure of such proteins. Ideally, that structure could be predicted from the sequence of amino acids that correspond to the code in the gene on the DNA. This remains a challenging problem in computational chemistry (Chapter 6), but a combination of experimental and theoretical techniques have advanced our understanding of structure and function in proteins. For example, x-ray methods can be used when a protein can be crystallized (although this is often difficult). Nuclear magnetic resonance (NMR) techniques can be used to probe the structure of proteins in solution. Many of the computational techniques are related to recent advances in sequencing of DNA. Bioinformatics includes computational chemistry with the goals of predicting function and three-dimensional shape directly from the amino acid sequence—by comparison with sequence, function, and structural information for other proteins (often from other organisms).

Knowing protein structure can provide direct benefits to human health. The precise molecular structure of a protein gives it great selectivity in distinguishing among substrates. Sometimes that activity can be blocked by molecules that are similar to the substrate but do not cause a reaction or response when bound to the protein.

For example, with the crystal structure of the aspartyl protease from human immundeficiency virus (HIV-1) in 1989 came the opportunity to design molecules to block this important enzyme that acts as a molecular scissors. HIV is the virus responsible for AIDS. Essential to viral replication, the HIV protease cuts long strands composed of many proteins into the functional proteins found in mature virus particles. This proteolysis occurs at the very end of the HIV replication cycle (Figure 7-1). The three-dimensional structural information derived from the x-ray crystal structure, combined with computer modeling techniques, allowed chemists to design potent, selective inhibitors of the protease enzyme (Figure 7-2).