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

ABSTRACT: Molecular dynamics (MD) simulations are an important and well-established tool for investigating RNA structural dynamics, but their accuracy relies heavily on the quality of the employed force field (ff). In this work, we present a comprehensive evaluation of widely used pair-additive and polarizable RNA ffs using the challenging UUCG tetraloop (TL) benchmark system. Extensive standard MD simulations, initiated from the NMR structure of the 14-mer UUCG TL, revealed that most ffs did not maintain the native state, instead favoring alternative loop conformations. Notably, three very recent variants of pair-additive ffs, OL3_CP-gHBfix21, DES-Amber, and OL3_R2.7, successfully preserved the native structure over a 10 × 20 μs time scale. To further

SUBMITTER: Mlynsky V 

PROVIDER: S-EPMC12020377 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature