The human genome project has already discovered millions of proteins (http://www.swissprot.com). The potential of the genome project can only be fully realized once we can assign, understand, manipulate, and predict the function of these new proteins (Sanchez and Sali, 1997; Frishman et al., 2000; Domingues et al., 2000). Predicting protein function generally requires knowledge of protein three-dimensional structure (Blundell et al., 1978;Weber, 1990), which is ultimately determined by protein sequence (Anfinsen, 1973). Protein structure determination using experimental methods such as X-ray crystallography or NMR spectroscopy is very time consuming (Johnson et al. 1994). To date, fewer than 2% of the known proteins have had their structures solved experimentally. In 2004, more than half a million new proteins were sequenced that almost doubled the efforts in the previous year, but only 5300 structures were solved. Although the rate of experimental structure determination will continue to increase, the number of newly discovered sequences grows much faster than the number of structures solved (see Fig. 10.1).


Homology Modeling Template Structure Rotamer Library Spatial Restraint Multiple Structure Alignment 
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© Springer 2007

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  • Zhexin Xiang

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