CONFORMATION AND DYNAMICS OF DIMERIC UREIDO-BALHIMYCIN

The conformation of the antibiotic ureido-balhimycin has been investig ated by proton nmr and refined with computer simulations. The dimeric structure of ureido-balhimycin was established by unambiguous identifi cation of 6 nuclear Overhauser effects (NOEs) as intermonomeric, out o f the total of 186 NOEs observed Via distance geometry calculations th e antiparallel orientation of the two monomers was demonstrated. Furth er refinement by molecular dynamics simulations provided the essential hydrogen bonds and aromatic interactions responsible for interfacial stabilization. The computational protocol illustrated here (distance g eometry to define the coarse topology and molecular dynamics for refin ement) should find general applicability in the study of homodimers. ( C) 1995 John Wiley & Sons, Inc.