Molecular simulations matching denaturation experiments for N6-Methyladenosine

Abstract: Post-transcriptional modifications are crucial for RNA function and can affect its structure and dynamics. Force-field based classical molecular dynamics simulations are a fundamental tool to characterize biomolecular dynamics and their application to RNA is flourishing. Here we show that the set of force-field parameters for N$^6$-methyladenosine (m$^6$A) developed for the commonly used AMBER force field does not reproduce duplex denaturation experiments and, specifically, cannot be used to describe both paired and unpaired states. Then we use reweighting techniques to derive new parameters matching available experimental data. The resulting force field can be used to properly describe paired and unpaired m$^6$A in both syn and anti conformation, and thus opens the way to the use of molecular simulations to investigate the effects of N6 methylations on RNA structural dynamics.