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Evaluation of Solvent Accessibility Epitopes for Different Dehydrogenase Inhibitors
Author(s) -
Ludwig Christian,
Michiels Paulus J. A.,
Lodi Alessia,
Ride John,
Bunce Chris,
Günther Ulrich L.
Publication year - 2008
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200800110
Subject(s) - magnetization , solvent , ligand (biochemistry) , chemistry , molecule , epitope , magnetization transfer , small molecule , computational chemistry , crystallography , combinatorial chemistry , stereochemistry , biochemistry , receptor , physics , biology , organic chemistry , antigen , magnetic field , radiology , medicine , quantum mechanics , magnetic resonance imaging , genetics
Knowledge about the orientation of ligands or inhibitors bound to a protein is vital for the development of new drugs. It was recently shown that solvent accessibility epitopes for protein ligands can be mapped by transferring magnetization from water molecules to the ligand to derive the ligand orientation. This is based on the fact that NMR signals of ligands arising from magnetization transferred from solvent molecules via the protein have a different sign from those arising from direct magnetization transfer from bulk water. Herein we critically evaluate the applicability of solvent accessibility mapping to derive binding orientations for ligands of two dehydrogenases (AKR1C3 and HSD17β1) with very different binding pockets, including complexes in which the ligand is buried more deeply inside the protein. We also evaluate the possibility of using co‐solvents, such as DMSO, for magnetization transfer.