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, which thus opens the way to the use of molecular simulations to investigate the effects of N-6 methylations on RNA structural dynamics.

Molecular Simulations Matching Denaturation Experiments for N-6-Methyladenosine / Piomponi, V; Froehlking, T; Bernetti, M; Bussi, G. - 8:8(2022), pp. 1218-1228. [10.1021/acscentsci.2c00565]

Molecular Simulations Matching Denaturation Experiments for N-6-Methyladenosine

Piomponi, V;Froehlking, T;Bernetti, M;Bussi, G
2022

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, which thus opens the way to the use of molecular simulations to investigate the effects of N-6 methylations on RNA structural dynamics.
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8
1218
1228
10.1021/acscentsci.2c00565
Piomponi, V; Froehlking, T; Bernetti, M; Bussi, G
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11767/129310
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