Supporting data for "FIREX: Fast-Ion Replica EXchange enables rapid sampling of Mg2+pairing with nucleic acids"

# Supplementary data for FIREX: Fast-Ion Replica EXchange enables rapid sampling of Mg²⁺ pairing with nucleic acids **Title publication:** *FIREX: Fast-Ion Replica EXchange enables rapid sampling of Mg²⁺ pairing with nucleic acids*** authors: L. Kantin, J. Puyo-Fourtine, J. Hénin, E. Duboué Dijon **DOI publication:** https://doi.org/10.26434/chemrxiv.15005591/v1 **Description:** Simulations of double-stranded DNA Dickerson–Drew Dodecamer (from structure PDB: 1NAJ) with 11 magnesium ions in water at temperature 300K and 1 bar. Some simulations were done with sodium chloride ions (150 mM KCl) as well. All HREX-q, FIREX, REST2-DNA, REST2-DNA-Mg, and FIREX-REST2 simulations were started from two initial configuration: etheir all magnesium ions in direct contact, all all unbound. **Force fields:** Two force fields were used: Amber-OL15 and its ECC 0.8 variant Amber-OL15-ECC and the water model used is TIP3P. In some simulations, magnesium ions charges were reduced from 2+ (or 1.6+ for Amber-OL15-ECC) down to 1+ (HREX-q or suffix "Mg-q1" in subfolders names), or as well the paire-specific Lennard-Jones well-depth parameter $\varepsilon_\text{Mg-OP}$ (FIREX, FIREX-REST2 or suffix "Mg-opt" in subfolders names). Force fields folders or standalone topologies are included. **Content:** Each folders contains all inputs required for reproducing the simulations and the processed trajectory without water, as well as README.txt containing the commands used to reproduce the simulations. The folder `eABF/` contains all inputs to reproduce all eABF calculations, and the folder `AlchemicalTransf/` contains sample files for the alchemical calculation of the Mg-DMP binding free energy. The calculation is performed in two legs, decoupling in water (0-Mg_water) and in the contact pair (1-Mg-DMP). Simulations (XTC format) are 500 ns (HREX-q, FIREX, REST2-DNA, REST2-DNA-Mg, and FIREX-REST2 ), 1 µs (plain MD), or ~200 ns long (*Mg-opt and Mg-q1). For all replica exchange MD, only the replica 0 trajectories are given. Other README.txt files can be found in HREX-q, FIREX and FIREX-REST2 folders containing mapping of magnesium parameters with replica indices. Scripts used to compute the magnesium-phosphate distance, edit the topologies for FIREX-REST2 simulations, to reproduce the figures, and compute the binding free energy from alchemical transformation are available in `script/`. All folders are named based of Table SI 7, reported below: ## Simulation Summary (SI 7) | System | Simulation type | Force field | Simulation length ||---|---|---|---|| DDD, 11 Mg²⁺ ions | plain MD | Amber-OL15 | 2 (start) × 1 μs × 3 replicas || DDD, 11 Mg²⁺ ions | plain MD | Amber-OL15-ECC | 2 (start) × 1 μs × 3 replicas || DDD, 11 Mg²⁺ ions | HREX(q) | Amber-OL15 | 2 (start) × 34 (repl.) × 500 ns || DDD, 11 Mg²⁺ ions | HREX(q) | Amber-OL15-ECC | 2 (start) × 21 (repl.) × 500 ns || DDD, 11 Mg²⁺ ions | FIREX | Amber-OL15 | 2 (start) × 34 (repl.) × 500 ns || DDD, 11 Mg²⁺ ions | FIREX | Amber-OL15-ECC | 2 (start) × 21 (repl.) × 500 ns || DDD, 11 Mg²⁺ ions, 150 mM KCl | plain MD | Amber-OL15 | 2 (start) × 1 μs × 3 replicas || DDD, 11 Mg²⁺ ions, 150 mM KCl | plain MD | Amber-OL15-ECC | 2 (start) × 1 μs × 3 replicas || DDD, 11 Mg²⁺ ions, 150 mM KCl | REST2(DNA) | Amber-OL15 | 2 (start) × 12 (repl.) × 500 ns || DDD, 11 Mg²⁺ ions, 150 mM KCl | REST2(DNA) | Amber-OL15-ECC | 2 (start) × 12 (repl.) × 500 ns || DDD, 11 Mg²⁺ ions, 150 mM KCl | REST2(DNA,Mg) | Amber-OL15 | 2 (start) × 12 (repl.) × 500 ns || DDD, 11 Mg²⁺ ions, 150 mM KCl | REST2(DNA,Mg) | Amber-OL15-ECC | 2 (start) × 12 (repl.) × 500 ns || DDD, 11 Mg²⁺ ions, 150 mM KCl | FIREX+REST2 | Amber-OL15 | 2 (start) × 32 (repl.) × 500 ns || DDD, 11 Mg²⁺ ions, 150 mM KCl | FIREX+REST2 | Amber-OL15-ECC | 2 (start) × 24 (repl.) × 500 ns | *List of simulated systems (DDD = Dickerson–Drew Dodecamer) for each force field and computational setup (plain MD, REST2, HREX(q), FIREX, FIREX+REST2), together with the total simulation time (including the number of different starting points and the number of replicas in HREX schemes).*