| The Protein Structure Initiative, a project on the scale of the Human Genome Project aimed at protein structure determination, has successfully identified the structure of multiple human proteins. Unfortunately, knowledge of structure alone provides little insight into a protein's function within the body. A protein's function is defined by its active site, the area of the protein structure involved in the chemistry of its function. Because a protein's structure is related to its sequence, there currently exist many methods which compare protein sequences in an attempt to extrapolate function. Although effective for specific cases, there exist many documented instances where two proteins have similar structure and function, but dissimilar sequences. This occurs because structure determines the functionality of the protein, not the sequence.;A tool called PASSS was developed to compare and find similarities between the three dimensional structures of protein active sites. This application performs three main tasks, which include providing an automated routine for extracting protein structural information from the Protein Data Bank, utilizing a database for efficient local retrieval of the structural information, and finally implementing algorithms for protein active site comparison. Results from this application illustrate that PASSS is able to identify proteins that are functionally related to a known protein. This tool will be useful in structural genomics initiatives and medical science where knowing the active site structure will assist in identifying molecules that can either inhibit or activate a protein. This type of knowledge is particularly important in drug discovery. |
