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Ligand Binding Site Detection b Local Structure Alignment and Its Performance Complementarity
Lee, Hui Sun Im, Wonpil
Lee, Hui Sun
Im, Wonpil
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Abstract
Accurate determination of potential ligand binding sites (BS) is a key step for protein function characterization and structure-based drug design. Despite promising results of template-based BS prediction methods using global structure alignment (GSA), there is a room to improve the performance by properly incorporating local structure alignment (LSA) because BS are local structures and often similar for proteins with dissimilar global folds. We present a template-based ligand BS prediction method using G-LoSA, our LSA tool. A large benchmark set validation shows that G-LoSA predicts drug-like ligands’ positions in single-chain protein targets more precisely than TM-align, a GSA-based method, while the overall success rate of TM-align is better. G-LoSA is particularly efficient for accurate detection of local structures conserved across proteins with diverse global topologies. Recognizing the performance complementarity of G-LoSA to TM-align and a non-template geometry-based method, fpocket, a robust consensus scoring method, CMCS-BSP (Complementary Methods and Consensus Scoring for ligand Binding Site Prediction), is developed and shows improvement on prediction accuracy. The G-LoSA source code is freely available at http://im.bioinformatics.ku.edu/GLoSA.
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Date
2013-09-23
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American Chemical Society
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Keywords
Template-based method, G-LoSA, Global structure alignment, Pocket shape, Computer-aided drug design
Citation
Lee, H. S., & Im, W. (2013). Ligand Binding Site Detection by Local Structure Alignment and Its Performance Complementarity. Journal of Chemical Information and Modeling, 53(9), 10.1021/ci4003602. http://doi.org/10.1021/ci4003602