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

We added parameters to the AMBER* force field to model cyclic beta-amino ac id derivatives moro accurately within the commonly used MacroModel program. In an effort to generate an improved treatment of cyclohexane and cyclopen tane conformational preferences, carbon-carbon torsional parameters were mo dified and incorporated into a force field we call AMBER*C. Simulation of t raits 2-aminocyclohexanecarboxylic acid (trans-ACHC) and trans-2-aminocyclo pentanecarboxylic acid (trans-ACPC) derivatives using AMBER*C produces more realistic energy differences between (pseudo)diaxial and (pseudo)diequator ial conformations than does simulation using AMBER*. AMBER*C molecular dyna mics simulations more accurately reproduce the experimental hydrogen-bondin g tendencies of simple diamide derivatives of trans-ACHC and trans-ACPC tha n do simulations using the AMBER* force field. More importantly, this modif ied force field allows accurate qualitative prediction of the helical secon dary structures adopted by beta-amino acid homo-oligomers. (C) 2000 John Wi lely & Sons, Inc.