Computer-assisted study and design of non-natural peptidomimetics
is increasingly important in the development of novel constructs with
widespread applicability. Among these methods, molecular dynamics
can accurately describe monomeric as well as oligomeric states of
these compounds. We studied seven different sequences composed of
cyclic and acyclic β-amino acids, the closest homologues of
natural peptides, and compared the performance on them of three force
field families in which specific modifications were made to improve
reproduction of β-peptide structures. Altogether 17 systems
were simulated, each for 500 ns, testing multiple starting conformations
and in three cases also oligomer formation and stability from eight
β-peptide monomers. The results indicated that our recently
developed CHARMM force field extension, based on torsional energy
path matching of the β-peptide backbone against quantum-chemical
calculations, performs best overall, reproducing the experimental
structures accurately in all monomeric simulations and correctly describing
all the oligomeric examples. The Amber and GROMOS force fields could
only treat some of the seven peptides (four in each case) without
further parametrization. Amber was able to reproduce the experimental
secondary structure of those β-peptides which contained cyclic
β-amino acids, while the GROMOS force field had the lowest performance
in this sense. From the latter two, Amber was able to hold together
already formed associates in the prepared state but was not able to
yield spontaneous oligomer formation in the simulations.