3ht9 | pdb_00003ht9

2-methoxyphenol in complex with T4 lysozyme L99A/M102Q

spinqualitylabelsall models 3ht9, resolution 2.02Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3ht9 is a 1 chain structure with sequence from Enterobacteria phage t4. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BME, JZ3, PO4 Related: 1lgu, 3ht6, 3ht7, 3ht8, 3htb, 3htd, 3htf, 3htg, 3hu8, 3hu9, 3hua, 3huk, 3huq Gene: E (Enterobacteria phage T4) Activity: Lysozyme, with EC number 3.2.1.17 Resources: FirstGlance, OCA, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed We present a combined experimental and modeling study of organic ligand molecules binding to a slightly polar engineered cavity site in T4 lysozyme (L99A/M102Q). For modeling, we computed alchemical absolute binding free energies. These were blind tests performed prospectively on 13 diverse, previously untested candidate ligand molecules. We predicted that eight compounds would bind to the cavity and five would not; 11 of 13 predictions were correct at this level. The RMS error to the measurable absolute binding energies was 1.8 kcal/mol. In addition, we computed "relative" binding free energies for six phenol derivatives starting from two known ligands: phenol and catechol. The average RMS error in the relative free energy prediction was 2.5 kcal/mol (phenol) and 1.1 kcal/mol (catechol). To understand these results at atomic resolution, we obtained x-ray co-complex structures for nine of the diverse ligands and for all six phenol analogs. The average RMSD of the predicted pose to the experiment was 2.0 A (diverse set), 1.8 A (phenol-derived predictions), and 1.2 A (catechol-derived predictions). We found that predicting accurate affinities and rank-orderings required near-native starting orientations of the ligand in the binding site. Unanticipated binding modes, multiple ligand binding, and protein conformational change all proved challenging for the free energy methods. We believe that these results can help guide future improvements in physics-based absolute binding free energy methods. Predicting ligand binding affinity with alchemical free energy methods in a polar model binding site.,Boyce SE, Mobley DL, Rocklin GJ, Graves AP, Dill KA, Shoichet BK J Mol Biol. 2009 Dec 11;394(4):747-63. Epub 2009 Sep 24. PMID:19782087 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Lysozyme 3D structures

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