A threading-based method (FINDSITE) for ligand-binding site prediction and functional annotation

@article{citeulike:2180805, abstract = {The detection of ligand-binding sites is often the starting point for protein function identification and drug discovery. Because of inaccuracies in predicted protein structures, extant binding pocket-detection methods are limited to experimentally solved structures. Here, FINDSITE, a method for ligand-binding site prediction and functional annotation based on binding-site similarity across groups of weakly homologous template structures identified from threading, is described. For crystal structures, considering a cutoff distance of 4 A as the hit criterion, the success rate is 70.9\% for identifying the best of top five predicted ligand-binding sites with a ranking accuracy of 76.0\%. Both high prediction accuracy and ability to correctly rank identified binding sites are sustained when approximate protein models (<35\% sequence identity to the closest template structure) are used, showing a 67.3\% success rate with 75.5\% ranking accuracy. In practice, FINDSITE tolerates structural inaccuracies in protein models up to a rmsd from the crystal structure of 810 A. This is because analysis of weakly homologous protein models reveals that about half have a rmsd from the native binding site <2 A. Furthermore, the chemical properties of template-bound ligands can be used to select ligand templates associated with the binding site. In most cases, FINDSITE can accurately assign a molecular function to the protein model. 10.1073/pnas.0707684105}, author = {Brylinski, Michal and Skolnick, Jeffrey }, citeulike-article-id = {2180805}, doi = {http://dx.doi.org/10.1073/pnas.0707684105}, journal = {Proceedings of the National Academy of Sciences}, keywords = {annotation, binding, prediction, site, structure, threading}, month = {December}, pages = {0707684105+}, posted-at = {2008-01-10 01:30:18}, priority = {2}, title = {A threading-based method (FINDSITE) for ligand-binding site prediction and functional annotation}, url = {http://dx.doi.org/10.1073/pnas.0707684105}, year = {2007} }

TY - JOUR ID - citeulike:2180805 L3 - citeulike-article-id:2180805 TI - A threading-based method (FINDSITE) for ligand-binding site prediction and functional annotation JF - Proceedings of the National Academy of Sciences SP - 0707684105 N2 - The detection of ligand-binding sites is often the starting point for protein function identification and drug discovery. Because of inaccuracies in predicted protein structures, extant binding pocket-detection methods are limited to experimentally solved structures. Here, FINDSITE, a method for ligand-binding site prediction and functional annotation based on binding-site similarity across groups of weakly homologous template structures identified from threading, is described. For crystal structures, considering a cutoff distance of 4 A as the hit criterion, the success rate is 70.9% for identifying the best of top five predicted ligand-binding sites with a ranking accuracy of 76.0%. Both high prediction accuracy and ability to correctly rank identified binding sites are sustained when approximate protein models (<35% sequence identity to the closest template structure) are used, showing a 67.3% success rate with 75.5% ranking accuracy. In practice, FINDSITE tolerates structural inaccuracies in protein models up to a rmsd from the crystal structure of 810 A. This is because analysis of weakly homologous protein models reveals that about half have a rmsd from the native binding site <2 A. Furthermore, the chemical properties of template-bound ligands can be used to select ligand templates associated with the binding site. In most cases, FINDSITE can accurately assign a molecular function to the protein model. 10.1073/pnas.0707684105 KW - annotation KW - binding KW - prediction KW - site KW - structure KW - threading AU - Brylinski, Michal AU - Skolnick, Jeffrey PY - 2007/12/28/ UR - http://dx.doi.org/10.1073/pnas.0707684105 ER -