DOCK 6: combining techniques to model RNA-small molecule complexes. Export

@article{citeulike:4503247, abstract = {With an increasing interest in RNA therapeutics and for targeting RNA to treat disease, there is a need for the tools used in protein-based drug design, particularly DOCKing algorithms, to be extended or adapted for nucleic acids. Here, we have compiled a test set of RNA-ligand complexes to validate the ability of the DOCK suite of programs to successfully recreate experimentally determined binding poses. With the optimized parameters and a minimal scoring function, 70\% of the test set with less than seven rotatable ligand bonds and 26\% of the test set with less than 13 rotatable bonds can be successfully recreated within 2 A heavy-atom RMSD. When DOCKed conformations are rescored with the implicit solvent models AMBER generalized Born with solvent-accessible surface area (GB/SA) and Poisson-Boltzmann with solvent-accessible surface area (PB/SA) in combination with explicit water molecules and sodium counterions, the success rate increases to 80\% with PB/SA for less than seven rotatable bonds and 58\% with AMBER GB/SA and 47\% with PB/SA for less than 13 rotatable bonds. These results indicate that DOCK can indeed be useful for structure-based drug design aimed at RNA. Our studies also suggest that RNA-directed ligands often differ from typical protein-ligand complexes in their electrostatic properties, but these differences can be accommodated through the choice of potential function. In addition, in the course of the study, we explore a variety of newly added DOCK functions, demonstrating the ease with which new functions can be added to address new scientific questions.}, author = {Lang, P. Therese and Brozell, Scott R. and Mukherjee, Sudipto and Pettersen, Eric F. and Meng, Elaine C. and Thomas, Veena and Rizzo, Robert C. and Case, David A. and James, Thomas L. and Kuntz, Irwin D.}, citeulike-article-id = {4503247}, citeulike-linkout-0 = {http://dx.doi.org/10.1261/rna.1563609}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19369428}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19369428}, day = {15}, doi = {10.1261/rna.1563609}, issn = {1469-9001}, journal = {RNA (New York, N.Y.)}, keywords = {rna}, month = {June}, number = {6}, pages = {1219--1230}, posted-at = {2009-05-11 19:06:53}, priority = {2}, title = {DOCK 6: combining techniques to model RNA-small molecule complexes.}, url = {http://dx.doi.org/10.1261/rna.1563609}, volume = {15}, year = {2009} }

TY - JOUR ID - citeulike:4503247 L3 - citeulike-article-id:4503247 N2 - With an increasing interest in RNA therapeutics and for targeting RNA to treat disease, there is a need for the tools used in protein-based drug design, particularly DOCKing algorithms, to be extended or adapted for nucleic acids. Here, we have compiled a test set of RNA-ligand complexes to validate the ability of the DOCK suite of programs to successfully recreate experimentally determined binding poses. With the optimized parameters and a minimal scoring function, 70% of the test set with less than seven rotatable ligand bonds and 26% of the test set with less than 13 rotatable bonds can be successfully recreated within 2 A heavy-atom RMSD. When DOCKed conformations are rescored with the implicit solvent models AMBER generalized Born with solvent-accessible surface area (GB/SA) and Poisson-Boltzmann with solvent-accessible surface area (PB/SA) in combination with explicit water molecules and sodium counterions, the success rate increases to 80% with PB/SA for less than seven rotatable bonds and 58% with AMBER GB/SA and 47% with PB/SA for less than 13 rotatable bonds. These results indicate that DOCK can indeed be useful for structure-based drug design aimed at RNA. Our studies also suggest that RNA-directed ligands often differ from typical protein-ligand complexes in their electrostatic properties, but these differences can be accommodated through the choice of potential function. In addition, in the course of the study, we explore a variety of newly added DOCK functions, demonstrating the ease with which new functions can be added to address new scientific questions. IS - 6 JF - RNA (New York, N.Y.) SN - 1469-9001 EP - 1230 TI - DOCK 6: combining techniques to model RNA-small molecule complexes. VL - 15 SP - 1219 KW - rna AU - Lang, Therese AU - Brozell, Scott AU - Mukherjee, Sudipto AU - Pettersen, Eric AU - Meng, Elaine AU - Thomas, Veena AU - Rizzo, Robert AU - Case, David AU - James, Thomas AU - Kuntz, Irwin PY - 2009/06/15/ UR - http://dx.doi.org/10.1261/rna.1563609 ER -