ct8b00955_si_003.zip (39.76 kB)
Improving the Performance of the Amber RNA Force Field by Tuning the Hydrogen-Bonding Interactions
dataset
posted on 2019-03-21, 00:00 authored by Petra Kührová, Vojtěch Mlýnský, Marie Zgarbová, Miroslav Krepl, Giovanni Bussi, Robert B. Best, Michal Otyepka, Jiří Šponer, Pavel BanášMolecular dynamics (MD) simulations
became a leading tool for investigation of structural dynamics of
nucleic acids. Despite recent efforts to improve the empirical potentials
(force fields, ffs), RNA ffs have persisting deficiencies, which hamper
their utilization in quantitatively accurate simulations. Previous
studies have shown that at least two salient problems contribute to
difficulties in the description of free-energy landscapes of small
RNA motifs: (i) excessive stabilization of the unfolded single-stranded
RNA ensemble by intramolecular base–phosphate and sugar–phosphate
interactions and (ii) destabilization of the native folded state by
underestimation of stability of base pairing. Here, we introduce a
general ff term (gHBfix) that can selectively fine-tune nonbonding
interaction terms in RNA ffs, in particular, the H bonds. The gHBfix
potential affects the pairwise interactions between all possible pairs
of the specific atom types, while all other interactions remain intact;
i.e., it is not a structure-based model. In order to probe the ability
of the gHBfix potential to refine the ff nonbonded terms, we performed
an extensive set of folding simulations of RNA tetranucleotides and
tetraloops. On the basis of these data, we propose particular gHBfix
parameters to modify the AMBER RNA ff. The suggested parametrization
significantly improves the agreement between experimental data and
the simulation conformational ensembles, although our current ff version
still remains far from being flawless. While attempts to tune the
RNA ffs by conventional reparametrizations of dihedral potentials
or nonbonded terms can lead to major undesired side effects, as we
demonstrate for some recently published ffs, gHBfix has a clear promising
potential to improve the ff performance while avoiding introduction
of major new imbalances.