Molecular Dynamics Simulation of the Proline Conformational Equilibrium and Dynamics in Antamanide Using the CHARMM Force Field

The recently developed atomic force field parameter set CHARMM 22.0.β is used for Langevin dynamics (LD) simulations that probe the motional characteristics of the four proline residues in the cyclic decapeptide antamanide in chloroform. Seven 2-ns trajectories were computed to sample the proline pucker motion for different backbone conformations. Most of the calculated ³J_HH coupling constants and carbon-13 T₁ relaxation parameters, obtained by averaging over the conformations from the simulation data, are in nearly quantitative agreement with the experimental results obtained by NMR investigations of antamanide in chloroform solution (Mádi, Z. L.; Griesinger, C.; Ernst, R. R. J. Am. Chem. Soc. 1990, 112, 2908–2914). Within experimental accuracy, the equilibrium geometries deduced from NMR measurements are reproduced for all proline residues. Proline-2 and proline-7 sample two pucker conformations (C_β-endo/C_γ-exo and C_β-exo/C_γ-endo) on a picosecond time scale. In contrast, proline-3 and proline-8 are predominantly in the C_β-exo/C_γ-endo conformation with the endocyclic torsion angle χ₂ being negative, in agreement with experiment. The LD simulation indicates that the mobility of the proline ring moiety depends on the value of its φ dihedral angle, in accord with analyses based on structural data (Cung, M. T.; Vitoux, B.; Marraud, M. New. J. Chem. 1987, 11, 503–510). Comparison of the GROMOS united-atom potential results (Brunne, R. M.; van Gunsteren, W. F.; Brüschweiler, R.; Ernst, R. R. J. Am. Chem. Soc. 1993, 115, 4764–4768) with those from the CHARMM all-atom potential shows that both force fields represent adequately the equilibrium conformations while CHARMM 22 describes more accurately dynamic properties of the prolines in this system.