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

0583260 - BFÚ 2024 RIV US eng J - Článek v odborném periodiku
Mlýnský, Vojtech - Kührová, Petra - Stadlbauer, Petr - Krepl, Miroslav - Otyepka, M. - Banáš, Pavel - Šponer, Jiří
Simple Adjustment of Intranucleotide Base-Phosphate Interaction in the OL3 AMBER Force Field Improves RNA Simulations.
Journal of Chemical Theory and Computation. Roč. 19, č. 22 (2023), s. 8423-8433. ISSN 1549-9618. E-ISSN 1549-9626
Grant CEP: GA ČR(CZ) GA23-05639S
Institucionální podpora: RVO:68081707
Klíčová slova: molecular-dynamics simulations * replica exchange * parameters * tetraloops * uucg * nmr * resolution
Obor OECD: Atomic, molecular and chemical physics (physics of atoms and molecules including collision, interaction with radiation, magnetic resonances, Mössbauer effect)
Impakt faktor: 5.5, rok: 2022
Způsob publikování: Open access
https://pubs.acs.org/doi/10.1021/acs.jctc.3c00990

Molecular dynamics (MD) simulations represent an established tool to study RNA molecules. The outcome of MD studies depends, however, on the quality of the force field (ff). Here we suggest a correction for the widely used AMBER OL3 ff by adding a simple adjustment of the nonbonded parameters. The reparameterization of the Lennard-Jones potential for theH8<middle dot><middle dot><middle dot>O5 '- andH6<middle dot><middle dot><middle dot>O5 '- atom pairs addresses an intranucleotide steric clash occurring in the type 0 base-phosphate interaction (0BPh). The nonbonded fix (NBfix) modification of 0BPh interactions (NBfix(0BPh) modification) was tuned via a reweighting approach and subsequently tested using an extensive set of standard and enhanced sampling simulations of both unstructured and folded RNA motifs. The modification corrects minor but visible intranucleotide clash for the anti nucleobase conformation. We observed that structural ensembles of small RNA benchmark motifs simulated with the NBfix(0BPh) modification provide better agreement with experiments. No side effects of the modification were observed in standard simulations of larger structured RNA motifs. We suggest that the combination of OL3 RNA ff and NBfix(0BPh) modification is a viable option to improve RNA MD simulations.
Trvalý link: https://hdl.handle.net/11104/0351262