Jiří Šponer

Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 612 00, Brno, Czech Republic

Atomistic Molecular Dynamics Simulations of Nucleic Acids: Force Field Advances and Issues

Abstract Atomistic molecular dynamics (MD) simulations are an important tool for understanding the structural dynamics of nucleic acids and their complexes with proteins and ligands. I will provide a brief overview of our recent MD studies of selected systems, including interactions of RNA recognition motif protein domains with single-stranded RNA and the basic principles governing the folding landscapes of guanine quadruplex structures. I will then place particular emphasis on the limitations of atomistic MD, namely persistent force-field uncertainties and the often underestimated limitations of collective-variable–based enhanced sampling protocols. Finally, I will comment on recent developments in the OL series of modifications of AMBER nucleic acid force fields, discuss how simulation outcomes depend on the choice of water model, and rationalize why it can sometimes be justified to use goal-specific force-field modifications that sacrifice broad transferability in favor of accurately describing a specific class of nucleic acid systems.

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