Proteomics and Drug Discovery
One of the most promising developments to come from the study of human genes and proteins has been the identification of potential new drugs for the treatment of disease. This relies on genome and proteome information to identify proteins associated with a disease, which computer software can then use as targets for new drugs. For example, if a certain protein is implicated in a disease, the 3D structure of that protein provides the information a computer programs needs to design drugs to interfere with the action of the protein. A molecule that fits the active site of an enzyme, but cannot be released by the enzyme, will inactivate the enzyme. This is the basis of new drug-discovery tools, which aim to find new drugs to inactivate proteins involved in disease. As genetic differences among individuals are found, researchers will use these same techniques to develop personalized drugs that are more effective for the individual.
Virtual ligand screening is a computer technique that attempts to fit millions of small molecules to the three-dimensional structure of a protein. The computer rates the quality of the fit to various sites in the protein, with the goal of either enhancing or disabling the function of the protein, depending on its function in the cell. A good example of this is the identification of new drugs to target and inactivate the HIV-1 protease. The HIV-1 protease is an enzyme that cleaves a very large HIV protein into smaller, functional proteins. The virus cannot survive without this enzyme; therefore, it is one of the most effective protein targets for killing HIV
(Fig. 6).
Because many proteins have multiple functions, it may be necessary to develop drugs for each function of a multitask protein. In addition, most proteins act as part of complexes and networks, which may also affect the way a protein acts in a cell. This may also affect the ability of drugs to disable the protein. Understanding the proteome, the structure and function of each protein, and the complexities of protein-protein interactions will be critical for developing the most effective diagnostic techniques and disease treatments in the future.
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