6bf3

Solution structure of de novo macrocycle design7.3a

spinqualitylabelsall models 6bf3 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6bf3 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: DAS, DPR, DTH Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Mixed-chirality peptide macrocycles such as cyclosporine are among the most potent therapeutics identified to date, but there is currently no way to systematically search the structural space spanned by such compounds. Natural proteins do not provide a useful guide: Peptide macrocycles lack regular secondary structures and hydrophobic cores, and can contain local structures not accessible with l-amino acids. Here, we enumerate the stable structures that can be adopted by macrocyclic peptides composed of l- and d-amino acids by near-exhaustive backbone sampling followed by sequence design and energy landscape calculations. We identify more than 200 designs predicted to fold into single stable structures, many times more than the number of currently available unbound peptide macrocycle structures. Nuclear magnetic resonance structures of 9 of 12 designed 7- to 10-residue macrocycles, and three 11- to 14-residue bicyclic designs, are close to the computational models. Our results provide a nearly complete coverage of the rich space of structures possible for short peptide macrocycles and vastly increase the available starting scaffolds for both rational drug design and library selection methods. Comprehensive computational design of ordered peptide macrocycles.,Hosseinzadeh P, Bhardwaj G, Mulligan VK, Shortridge MD, Craven TW, Pardo-Avila F, Rettie SA, Kim DE, Silva DA, Ibrahim YM, Webb IK, Cort JR, Adkins JN, Varani G, Baker D Science. 2017 Dec 15;358(6369):1461-1466. doi: 10.1126/science.aap7577. PMID:29242347 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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