COMBINED USE OF HOMONUCLEAR AND HETERONUCLEAR COUPLING-CONSTANTS AS RESTRAINTS IN MOLECULAR-DYNAMICS SIMULATIONS

A penalty function for scalar coupling constants has been applied in molecular dynamics simulations as an experimental constraint. The function is based on the difference between the coupling constant calculated from the dihedral angle and the experimentally measured coupling constant. The method is illustrated on a model cyclic pentapeptide for which 3J(HN-H-alpha) and 3J(HN-C-beta), both about the phi-backbone dihedral angle, have been measured. The function is efficient in producing structures consistent with the scalar couplings, but removed from the conformation observed in solution. This arises from the lack of J restraints for the psi-dihedral angle. Simulations with both nuclear Overhauser effect (NOE) and J-coupling restraints illustrates small but significant differences from simulations using only NOEs.