2OTY
1,2-dichlorobenzene in complex with T4 Lysozyme L99A
2OTY の概要
| エントリーDOI | 10.2210/pdb2oty/pdb |
| 関連するPDBエントリー | 181L |
| 分子名称 | Lysozyme, PHOSPHATE ION, BETA-MERCAPTOETHANOL, ... (5 entities in total) |
| 機能のキーワード | hydrolase, protein-ligand complex, model system |
| 由来する生物種 | Enterobacteria phage T4 |
| 細胞内の位置 | Host cytoplasm : P00720 |
| タンパク質・核酸の鎖数 | 1 |
| 化学式量合計 | 18869.07 |
| 構造登録者 | |
| 主引用文献 | Mobley, D.L.,Graves, A.P.,Chodera, J.D.,McReynolds, A.C.,Shoichet, B.K.,Dill, K.A. Predicting absolute ligand binding free energies to a simple model site. J.Mol.Biol., 371:1118-1134, 2007 Cited by PubMed Abstract: A central challenge in structure-based ligand design is the accurate prediction of binding free energies. Here we apply alchemical free energy calculations in explicit solvent to predict ligand binding in a model cavity in T4 lysozyme. Even in this simple site, there are challenges. We made systematic improvements, beginning with single poses from docking, then including multiple poses, additional protein conformational changes, and using an improved charge model. Computed absolute binding free energies had an RMS error of 1.9 kcal/mol relative to previously determined experimental values. In blind prospective tests, the methods correctly discriminated between several true ligands and decoys in a set of putative binders identified by docking. In these prospective tests, the RMS error in predicted binding free energies relative to those subsequently determined experimentally was only 0.6 kcal/mol. X-ray crystal structures of the new ligands bound in the cavity corresponded closely to predictions from the free energy calculations, but sometimes differed from those predicted by docking. Finally, we examined the impact of holding the protein rigid, as in docking, with a view to learning how approximations made in docking affect accuracy and how they may be improved. PubMed: 17599350DOI: 10.1016/j.jmb.2007.06.002 主引用文献が同じPDBエントリー |
| 実験手法 | X-RAY DIFFRACTION (1.83 Å) |
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