High-Performance Drug Discovery: Computational Screening by Combining Docking and Molecular Dynamics Simulations Export

@article{citeulike:5917052, abstract = {Virtual compound screening using molecular docking is widely used in the discovery of new lead compounds for drug design. However, this method is not completely reliable and therefore unsatisfactory. In this study, we used massive molecular dynamics simulations of protein-ligand conformations obtained by molecular docking in order to improve the enrichment performance of molecular docking. Our screening approach employed the molecular mechanics/Poisson-Boltzmann and surface area method to estimate the binding free energies. For the top-ranking 1,000 compounds obtained by docking to a target protein, approximately 6,000 molecular dynamics simulations were performed using multiple docking poses in about a week. As a result, the enrichment performance of the top 100 compounds by our approach was improved by 1.6\^{a}€ ” 4.0 times that of the enrichment performance of molecular dockings. This result indicates that the application of molecular dynamics simulations to virtual screening for lead discovery is both effective and practical. However, further optimization of the computational protocols is required for screening various target proteins.}, author = {Okimoto, Noriaki and Futatsugi, Noriyuki and Fuji, Hideyoshi and Suenaga, Atsushi and Morimoto, Gentaro and Yanai, Ryoko and Ohno, Yousuke and Narumi, Tetsu and Taiji, Makoto}, citeulike-article-id = {5917052}, citeulike-linkout-0 = {http://dx.doi.org/10.1371/journal.pcbi.1000528}, day = {9}, doi = {10.1371/journal.pcbi.1000528}, journal = {PLoS Comput Biol}, keywords = {design, folding, microphysics}, month = {October}, number = {10}, pages = {e1000528+}, posted-at = {2009-10-11 14:30:18}, priority = {2}, publisher = {Public Library of Science}, title = {High-Performance Drug Discovery: Computational Screening by Combining Docking and Molecular Dynamics Simulations}, url = {http://dx.doi.org/10.1371/journal.pcbi.1000528}, volume = {5}, year = {2009} }

TY - JOUR ID - citeulike:5917052 L3 - citeulike-article-id:5917052 N2 - Virtual compound screening using molecular docking is widely used in the discovery of new lead compounds for drug design. However, this method is not completely reliable and therefore unsatisfactory. In this study, we used massive molecular dynamics simulations of protein-ligand conformations obtained by molecular docking in order to improve the enrichment performance of molecular docking. Our screening approach employed the molecular mechanics/Poisson-Boltzmann and surface area method to estimate the binding free energies. For the top-ranking 1,000 compounds obtained by docking to a target protein, approximately 6,000 molecular dynamics simulations were performed using multiple docking poses in about a week. As a result, the enrichment performance of the top 100 compounds by our approach was improved by 1.6–4.0 times that of the enrichment performance of molecular dockings. This result indicates that the application of molecular dynamics simulations to virtual screening for lead discovery is both effective and practical. However, further optimization of the computational protocols is required for screening various target proteins. IS - 10 JF - PLoS Comput Biol TI - High-Performance Drug Discovery: Computational Screening by Combining Docking and Molecular Dynamics Simulations PB - Public Library of Science VL - 5 SP - e1000528 KW - design KW - folding KW - microphysics AU - Okimoto, Noriaki AU - Futatsugi, Noriyuki AU - Fuji, Hideyoshi AU - Suenaga, Atsushi AU - Morimoto, Gentaro AU - Yanai, Ryoko AU - Ohno, Yousuke AU - Narumi, Tetsu AU - Taiji, Makoto PY - 2009/10/09/ UR - http://dx.doi.org/10.1371/journal.pcbi.1000528 ER -