INVESTIGATIONS OF PEPTIDE HYDRATION USING NMR AND MOLECULAR-DYNAMICS SIMULATIONS - A STUDY OF EFFECTS OF WATER ON THE CONFORMATION AND DYNAMICS OF ANTAMANIDE

The influence of water binding on the conformational dynamics of the c yclic decapeptide antamanide dissolved in the model lipophilic environ ment chloroform is investigated by NMR relaxation measurements. The wa ter-peptide complex has a lifetime of 35 mu s at 250 K, which is longe r than typical lifetimes of water-peptide complexes reported in aqueou s solution. In addition, there is a rapid intracomplex mobility that p robably involves librational motions of the bound water or water molec ules hopping between different binding sites. Water binding restricts the flexibility of antamanide. The experimental findings are compared with GROMOS molecular dynamics simulations of antamanide with up to ei ght bound water molecules. Within the simulation time of 600 ps, no wa ter molecule leaves the complex. Additionally, the simulations show a reduced flexibility for the complex in comparison with uncomplexed ant amanide. Thus, there is a qualitative agreement between the experiment al NMR results and the computer simulations.