4nvh

Predicting protein conformational response in prospective ligand discovery

spinqualitylabelsall models 4nvh, resolution 1.24Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4nvh is a 1 chain structure with sequence from Saccharomyces cerevisiae RM11-1a. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.24Å Ligands: 2NB, HEM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function B3LRE1_YEAS1 Publication Abstract from PubMed Proteins fluctuate between alternative conformations, which presents a challenge for ligand discovery because such flexibility is difficult to treat computationally owing to problems with conformational sampling and energy weighting. Here we describe a flexible docking method that samples and weights protein conformations using experimentally derived conformations as a guide. The crystallographically refined occupancies of these conformations, which are observable in an apo receptor structure, define energy penalties for docking. In a large prospective library screen, we identified new ligands that target specific receptor conformations of a cavity in cytochrome c peroxidase, and we confirm both ligand pose and associated receptor conformation predictions by crystallography. The inclusion of receptor flexibility led to ligands with new chemotypes and physical properties. By exploiting experimental measures of loop and side-chain flexibility, this method can be extended to the discovery of new ligands for hundreds of targets in the Protein Data Bank for which similar experimental information is available. Incorporation of protein flexibility and conformational energy penalties in docking screens to improve ligand discovery.,Fischer M, Coleman RG, Fraser JS, Shoichet BK Nat Chem. 2014 Jul;6(7):575-83. doi: 10.1038/nchem.1954. Epub 2014 May 25. PMID:24950326 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cytochrome c peroxidase 3D structures

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