Improved treatment of cyclic ?-amino acids and successful prediction of ?-peptide secondary structure using a modified force field: AMBER*C

We added parameters to the AMBER* force field to model cyclic β-amino acid derivatives more accurately within the commonly used MacroModel program. In an effort to generate an improved treatment of cyclohexane and cyclopentane conformational preferences, carbon–carbon torsional parameters were modified and incorporated into a force field we call AMBER*C. Simulation of trans-2-aminocyclohexanecarboxylic acid (trans-ACHC) and trans-2-aminocyclopentanecarboxylic acid (trans-ACPC) derivatives using AMBER*C produces more realistic energy differences between (pseudo)diaxial and (pseudo)diequatorial conformations than does simulation using AMBER*. AMBER*C molecular dynamics simulations more accurately reproduce the experimental hydrogen-bonding tendencies of simple diamide derivatives of trans-ACHC and trans-ACPC than do simulations using the AMBER* force field. More importantly, this modified force field allows accurate qualitative prediction of the helical secondary structures adopted by β-amino acid homo-oligomers. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 763–773, 2000