Peptide Conformation from Coupling Constants: Scalar Couplings as Restraints in MD Simulations

The question of how far one can go in the determination of conformation with the sole use of coupling constants as restraints in MD simulations was addressed. Couplings are being used ever more frequently as constraints as measuring heteronuclear long‐range coupling constants becomes easier. For this investigation, cyclosporin A, which has previously been extensively examined with NOE‐restrained simulations, is used as a model system. Many additional one‐and three‐bond coupling constants have been measured. The MD simulations were carried out with the addition of a potential‐energy penalty function based directly on the Karplus curve. It is shown that, for dihedral angles with more than one coupling, the restraints are very efficient, in agreement with the structure observed from NOEs. However, it turned out that the structure of CsA is not adequately described, when only J couplings are used.