Development of GROMOS-Compatible Parameter Set for Simulations of Chalcones and Flavonoids

Chalcones
and flavonoids constitute a large family of plant secondary
metabolites that have been explored as a potential source of novel
pharmaceutical products. While the simulation of these compounds by
molecular dynamics (MD) can be a valuable strategy to assess their
conformational properties and so further develop their role in drug
discovery, there are no set of force field parameters specifically
designed and experimentally validated for their conformational description
in condensed phase. So the current work developed a new parameter
set for MD simulations of these compounds’ main scaffolds under
GROMOS force field. We employed a protocol adjusting the atomic charges
and torsional parameters to the respective quantum mechanical derived
dipole moments and dihedrals rotational profiles, respectively. Experimental
properties of organic liquids were used as references to the calculated
values to validate the parameters. Additionally, metadynamics simulations
were performed to evaluate the conformational space of complex chalcones
and flavonoids, while NOE contacts during simulations were measured
and compared to experimental data. Accordingly, the employed protocol
allowed us to obtain force field parameters that reproduce well the
target data and may be expected to contribute in more accurate computational
studies on the biological/therapeutical role of such molecules.