Empirical force fields for biomolecular systems are usually derived from quantum chemistry calculations and validated against experimental data. We here show how it is possible to refine the full dihedral-angle potential of the Amber RNA force field by using solution NMR data as well as stability of known structural motifs. The procedure can be used to mix multiple systems and heterogeneous experimental information and crucially depends on a regularization term chosen with a cross-validation procedure. By fitting corrections to the dihedral angles on the order of less than 1 kJ/mol per angle, it is possible to increase the stability of difficult-to-fold RNA tetraloops by more than 1 order of magnitude.

Institute of Biophysics of the Czech Academy of Sciences Kralovopolska 135 Brno 612 65 Czech Republic

Regional Centre of Advanced Technologies and Materials Department of Physical Chemistry Faculty of Science Palacký University tř 17 listopadu 12 771 46 Olomouc Czech Republic

Scuola Internazionale Superiore di Studi Avanzati via Bonomea 265 34136 Trieste Italy

Structural Biology and NMR Laboratory and Linderstrøm Lang Centre for Protein Science Department of Biology University of Copenhagen DK 2200 Copenhagen Denmark

References provided by Crossref.org

Can We Ever Develop an Ideal RNA Force Field? Lessons Learned from Simulations of the UUCG RNA Tetraloop and Other Systems

Simple Adjustment of Intranucleotide Base-Phosphate Interaction in the OL3 AMBER Force Field Improves RNA Simulations

Automatic Learning of Hydrogen-Bond Fixes in the AMBER RNA Force Field