An accurate, sensitive, and scalable method to identify functional sites in protein structures. Export

@article{Yao03, abstract = {Functional sites determine the activity and interactions of proteins and as such constitute the targets of most drugs. However, the exponential growth of sequence and structure data far exceeds the ability of experimental techniques to identify their locations and key amino acids. To fill this gap we developed a computational Evolutionary Trace method that ranks the evolutionary importance of amino acids in protein sequences. Studies show that the best-ranked residues form fewer and larger structural clusters than expected by chance and overlap with functional sites, but until now the significance of this overlap has remained qualitative. Here, we use 86 diverse protein structures, including 20 determined by the structural genomics initiative, to show that this overlap is a recurrent and statistically significant feature. An automated ET correctly identifies seven of ten functional sites by the least favorable statistical measure, an...}, address = {Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza T921, Houston, TX 77030, USA.}, author = {Yao, H. and Kristensen, D. M. and Mihalek, I. and Sowa, M. E. and Shaw, C. and Kimmel, M. and Kavraki, L. and Lichtarge, O.}, citeulike-article-id = {388927}, editor = {04:00, 2003/01/28}, journal = {J Mol Biol}, keywords = {algorithm, evolutionary\_trace, functional\_sites, structure\_analysis}, month = {Feb}, number = {1}, posted-at = {2005-11-11 16:23:16}, priority = {2}, title = {An accurate, sensitive, and scalable method to identify functional sites in protein structures.}, volume = {326}, year = {2003} }

TY - JOUR ID - Yao03 L3 - citeulike-article-id:388927 N2 - Functional sites determine the activity and interactions of proteins and as such constitute the targets of most drugs. However, the exponential growth of sequence and structure data far exceeds the ability of experimental techniques to identify their locations and key amino acids. To fill this gap we developed a computational Evolutionary Trace method that ranks the evolutionary importance of amino acids in protein sequences. Studies show that the best-ranked residues form fewer and larger structural clusters than expected by chance and overlap with functional sites, but until now the significance of this overlap has remained qualitative. Here, we use 86 diverse protein structures, including 20 determined by the structural genomics initiative, to show that this overlap is a recurrent and statistically significant feature. An automated ET correctly identifies seven of ten functional sites by the least favorable statistical measure, an... IS - 1 JF - J Mol Biol AD - Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza T921, Houston, TX 77030, USA. TI - An accurate, sensitive, and scalable method to identify functional sites in protein structures. VL - 326 KW - algorithm KW - evolutionary_trace KW - functional_sites KW - structure_analysis AU - Yao, H AU - Kristensen, DM AU - Mihalek, I AU - Sowa, ME AU - Shaw, C AU - Kimmel, M AU - Kavraki, L AU - Lichtarge, O A2 - 04:00, 2003/01/28 PY - 2003/Feb 7// ER -