Multifaceted Computational Modeling in Glycoscience. Journal of Chemical Information and Modeling 2022, Article ASAP. Actives-Based Receptor Selection Strongly Increases the Success Rate in Structure-Based Drug Design and Leads to Identification of 22 Potent Cancer Inhibitors. Journal of Medicinal Chemistry 2022, Article ASAP. Design, Synthesis, and Pharmacological Evaluation of Second-Generation Soluble Adenylyl Cyclase (sAC, ADCY10) Inhibitors with Slow Dissociation Rates. Levin, Jochen Buck, Maria Kehr, Sandrine Coquille, Joop van den Heuvel, Clemens Steegborn, Makoto Fushimi, Efrat Finkin-Groner, Robert W. Michael Miller, Thomas Rossetti, Jacob Ferreira, Lubna Ghanem, Melanie Balbach, Navpreet Kaur, Lonny R.Exploring the NCS-382 Scaffold for CaMKIIα Modulation: Synthesis, Biochemical Pharmacology, and Biophysical Characterization of Ph-HTBA as a Novel High-Affinity Brain-Penetrant Stabilizer of the CaMKIIα Hub Domain. Solbak, Petrine Wellendorph, Bente Frølund. Shehata, Stine Juul Gauger, Carolina Veronesi, Louise Hamborg, Louise Thiesen, Jesper Bruus-Jensen, Johanne Schlieper Royssen, Ulrike Leurs, Anne Sofie G. This article is cited by 5609 publications. Glide is also found to be more accurate than the recently described Surflex method. Comparisons to published data on rms deviations show that Glide is nearly twice as accurate as GOLD and more than twice as accurate as FlexX for ligands having up to 20 rotatable bonds. Errors in geometry for the top-ranked pose are less than 1 Å in nearly half of the cases and are greater than 2 Å in only about one-third of them. Docking accuracy is assessed by redocking ligands from 282 cocrystallized PDB complexes starting from conformationally optimized ligand geometries that bear no memory of the correctly docked pose. Selection of the best docked pose uses a model energy function that combines empirical and force-field-based terms. The very best candidates are further refined via a Monte Carlo sampling of pose conformation in some cases, this is crucial to obtaining an accurate docked pose. In this search, an initial rough positioning and scoring phase that dramatically narrows the search space is followed by torsionally flexible energy optimization on an OPLS-AA nonbonded potential grid for a few hundred surviving candidate poses. Unlike other methods for docking ligands to the rigid 3D structure of a known protein receptor, Glide approximates a complete systematic search of the conformational, orientational, and positional space of the docked ligand.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |