Development of force field parameters for cyclopentane-modified peptide nucleic acids

CHARMM force field parameters were developed for cyclopentane-modified peptide nucleic acid (cpPNA) analogs. As in the original force field parameterization, a self-consistent step-wise optimization approach was taken that involved the iterative adjustments of internal and external parameters until convergence was obtained. The geometry parameters such as standard bond lengths and bond angles were obtained by reproducing ab initio gas-phase geometries of model compounds. The internal force constants used for stretch and bend deformations were optimized to fit the calculated vibrational spectra. Torsional parameters were modified to fit the rotational barriers about single bonds in model compounds. The partial atomic charges were optimized based on interaction energies of complexes between water and the model compound. Our parameterization accurately reproduced high-level quantum mechanical calculations. The parameters were validated by series of molecular dynamics simulations of cpPNA in explicit water. Together with the existing force field for nucleic acids, these parameters will enable simulations of cpPNA complexes with RNA and DNA.