| Abstract
| - A new set of AMBER* parameters for proline-containing peptides isreported based on the resultsof high level ab initio calculations for a model prolinedipeptide, 1. These new parameters correcta number of deficiencies in the previous parameters for proline, andMonte Carlo/stochastic dynamics(MC/SD) free energy simulations for 1 with the new parameterset give a good agreement withexperiment for both the degree of internal hydrogen bonding and thepopulation of the cis isomer.The new parameter set is also applied to a conformational study ofthe sequence Ac-(l)Pro-X-NHMein CHCl3, where X = Gly,(d/l)Ala,(d/l)Val,(d/l)Ser, and(d/l)Asn(N-Me).β-Turn formation isfavored by alternating chirality in our simulations so thed-residues in the “X” position alwaysshow higher β-turn populations. The enthalpic preference forβ-turns in CHCl3 is also reproducedin our simulations. Calculated absolute enthalpies are lower thanthose found experimentally,but the simulations do correctly reproduce the trends in enthalpicpreference for β-turn formationwith X = Gly > Ala > Val. Finally the new parameter set isapplied to a conformational search ofcyclo((d)Pro-(l)Pro-(d)Pro-(l)Pro)and is shown to reproduce the experimentally observedstructurehaving alternating cis and trans amidebonds.
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