Precise structural determination of weakly binding peptides by utilizing dihedral angle constraints |
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Authors: | Yumiko Mizukoshi Michiko Nagasu Ichio Shimada Hideo Takahashi |
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Institution: | (1) Biomedicinal Information Research Center (BIRC), National Institute of Advanced Industrial Science and Technology (AIST), Aomi 2-41-6, Koto-ku, Tokyo 135-0064, Japan;(2) Japan Biological Informatics Consortium (JBIC), Aomi 2-41-6, Koto-ku, Tokyo 135-0064, Japan;(3) Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan; |
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Abstract: | Structural determination of target-bound conformations of peptides is of primary importance for the optimization of peptide
ligands and peptide–mimetic design. In the structural determination of weakly binding ligands, transferred nuclear Overhauser
effect (TrNOE) methods have been widely used. However, not many distance constraints can be obtained from small peptide ligands
by TrNOE, especially for peptides bound to a target molecule in an extended conformation. Therefore, for precise structural
determination of weakly binding peptides, additional structural constraints are required. Here, we present a strategy to systematically
introduce dihedral angle constraints obtained from multiple transferred cross-correlated relaxation experiments and demonstrate
precise structures of weakly binding peptides. As a result, we could determine the bioactive conformations of phage-derived
peptide ligands and define their core binding motifs. |
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Keywords: | |
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