CONGO RED BOUND TO ALPHA-1-PROTEINASE INHIBITOR AS A MODEL OF SUPRAMOLECULAR LIGAND AND PROTEIN COMPLEX

The complex formation and structure of alpha-1-proteinase inhibitor wi th supramolecular ligand Congo Red was predicted using molecular mecha nics and molecular dynamics simulation. A seven-molecule Congo Red lig and was introduced to the cleft in beta-sheet ''A'' of an alpha-1-prot einase inhibitor in place of the peptide chain fragment (342-358) whic h occupies this locus in the cleaved form of the inhibitor. The striki ng similarity of Congo Red and peptide chain (342-358) insertion effec ts, observed by comparison of root mean square (r.m.s.)-distance plots as protein stability increased, confirmed the reliability of the cons tructed complex. The binding predicted theoretically for the one avail able cleft in the beta-sheet, limited to a few Congo Red molecules, wa s verified experimentally. alpha-1-proteinase inhibitor was chosen for this study because of the known natural instability of its beta-pleat ed sheet, but the model is believed to represent other Congo Red compl exes involving proteins whose accessibility for dye penetration may be triggered by function-derived structural alterations or may be genera ted in unfolding conditions. (C) 1998 Elsevier Science Ltd. All rights reserved.