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.be ta is used for Langevin dynamics (LD) simulations that probe the motio nal characteristics of the four proline residues in the cyclic decapep tide antamanide in chloroform. Seven 2-ns trajectories were computed t o sample the proline pucker motion for different backbone conformation s. Most of the calculated 3J(HH) coupling constants and carbon-13 T1 r elaxation parameters, obtained by averaging over the conformations fro m the simulation data, are in nearly quantitative agreement with the e xperimental results obtained by NMR investigations of antamanide in ch loroform solution (Madi, Z. L.; Griesinger, C.; Ernst, R. R. J. Am. Ch em. Soc. 1990, 112, 2908-2914). Within experimental accuracy, the equi librium geometries deduced from NMR measurements are reproduced for al l proline residues. Proline-2 and proline-7 sample two pucker conforma tions (C(beta)-endo/C(gamma)-exo and C(beta)-exo/C(gamma)-endo) on a p icosecond time scale. In contrast, proline-3 and proline-8 are predomi nantly in the C(beta)-exo/C(gamma)-endo conformation with the endocycl ic torsion angle chi2 being negative, in agreement with experiment. Th e LD simulation indicates that the mobility of the proline ring moiety depends on the value of its phi dihedral angle, in accord with analys es based on structural data (Cung, M. T.; Vitoux, B.; Marraud, M. New. J. Chem. 1987, 11, 503-510). Comparison of the GROMOS united-atom pot ential results (Brunne, R. M.; van Gunsteren, W. F.; Bruschweiler, 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 a dequately the equilibrium conformations while CHARMM 22 describes more accurately dynamic properties of the prolines in this system.