Angewandte Chemie International Edition
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Cover Picture (Angew. Chem. Int. Ed. Engl. 13/14/1997)
The cover picture shows the complex of the MeIle11 (yellow) variant of the immunosuppressive drug cyclosporin A (CsA, orange) bound to the protein cyclophilin (CyP, represented as a gray ribbon except for three protein residues in pink that make close contacts with MeIle11 (Phe113, Phe60, Met61)). The structure including the water molecules comes from Monte Carlo simulations by A. C. Pierce and W. L. Jorgensen, which have been used to study the energetic and structural effects of introducing “bumps” and “holes” into the complex. The left inset shows a surface rendering of the MeIle11 in contact with the three pink residues of CyP. The right inset shows that mutation of Phe113 to Ala opens a hole to accommodate the MeIle11 side chain better; two water molecules also enter the cavity. More about these studies is reported on pages 1466ff. The picture was generated by Dr. E. M. Duffy with the Sybyl (Tripos Associates, Inc.) and ChemEdit (D. Lim, Yale University) programs.