Empirical corrections to the Amber RNA force field with Target Metadynamics

TL;DR

This paper introduces an empirical correction method using Target Metadynamics to improve the Amber RNA force field, resulting in better agreement with experimental data for specific RNA tetranucleotides.

Contribution

It presents a systematic correction protocol for force-field refinement based on experimental backbone angle distributions in RNA.

Findings

Improved agreement with experimental data for pyrimidine-containing tetranucleotides.

Highlighting the importance of alpha and beta backbone angles in RNA conformations.

Corrections are not universally portable to all RNA systems.

Abstract

The computational study of conformational transitions in nucleic acids still faces many challenges. For example, in the case of single stranded RNA tetranucleotides, agreement between simulations and experiments is not satisfactory due to inaccuracies in the force fields commonly used in molecular dynamics simulations. We here use experimental data collected from high-resolution X-ray structures to attempt an improvement of the latest version of the AMBER force field. A modified metadynamics algorithm is used to calculate correcting potentials designed to enforce experimental distributions of backbone torsion angles. Replica-exchange simulations of tetranucleotides including these correcting potentials show significantly better agreement with independent solution experiments for the oligonucleotides containing pyrimidine bases. Although the proposed corrections do not seem to be portable to generic RNA systems, the simulations revealed the importance of the alpha and beta backbone angles on the modulation of the RNA conformational ensemble. The correction protocol presented here suggests a systematic procedure for force-field refinement.