Amino acid side-chain populations in aqueous and saline solution: bis-penicillamine enkephalin

The potentials of mean force (pmfs) for rotation around the chi 1 aromatic side-chain dihedrals of the zwitterionic bis-penicillamine enkephalin pentapeptide have been determined in both aqueous and saline solution. These side chains are known to be associated with the pharmacophore and their conformational populations are thought to be critical for activity. It is found that the association between chloride ions and the peptide in saline solution simulations has profound effects on the relative energies of the g-, g+, and t conformations, and also the barriers between them. Using the pmfs we have also calculated the respective Boltzmann-weighted 3J alpha beta vicinal coupling constants. The agreement between the calculated and experimentally determined coupling constants is poor for the pmf in pure water, but substantially improved for the pmf determined in saline solution. Reasons for these differences appear to be related to the experimental conditions.