Magnesium Ion–Water Coordination and Exchange in Biomolecular Simulations

Abstract

Magnesium ions have an important role in the structure and folding mechanism of ribonucleic systems. To properly simulate these biophysical processes, the applied molecular models should reproduce, among others, the kinetic properties of the ions in water solution. Here, we have studied the kinetics of the binding of magnesium ions with water molecules and nucleic acids systems using molecular dynamics simulation in detail. We have validated the parameters used in biomolecular force fields, such as AMBER and CHARMM, for Mg2+ ions, and also for the biological relevant ions, Na+, K+ and Ca2+ together with three different water models (TIP3P, SPC/E and TIP5P). The results show that Mg2+ ions have a slower exchange rate than Na+, K+ and Ca2+ in agreement with experimental trend, but the simulated value underestimates the experimentally observed Mg2+-water exchange rate with several orders of magnitudes, irrespective of force field and water model. A new set of parameters for Mg2+ was developed to reproduce the experimental kinetic data. This set also leads to better reproduction of structural data than existing models. We have applied the new parameters set to Mg2+ binding with a mono-phosphate model system and with the purine riboswitch, add A-riboswitch. In line with the Mg2+-water results, the newly developed parameters show a better description of the structure and kinetic of the Mg2+-phosphate 2 binding than all other models. The characterization of the ion binding to the riboswitch system shows that the new parameter set does not affect the global structure of the ribonucleic acid system or the number of ions involved in direct or indirect binding. A slight decrease in the number of water-bridged contacts between A-riboswitch and Mg2+ ion is observed. The results support the ability of the newly developed parameters to improve the kinetic description of the Mg2+ and phosphate ions and their applicability in nucleic acid simulation.

Loop–loop interaction in an adenine-sensing riboswitch: A molecular dynamics study

“…Note that NMR experiments showed no structural deformations of the purine riboswitch using Mg 2+ :RNA ratios as high as 20:1 . Under the choice simulation conditions, Mg-water exchange is on the order of milliseconds, and Mg indirect binding to RNA has an average time of 50 psec (Allnér et al 2012). …”

Effects of hydroxyapatite (0001) Ca2+/Mg2+substitution on adsorbedd-ribose ring puckering

“…18 Electrostatic charges for D-ribose were calculated for the minimal energy structures described in our previous work 11 using the Restrained Electrostatic Potential (RESP) method, 19,20 and Boltzmann averaged. Force-field parameters for Ca 2+ and Mg 2+ were taken from Bradbrook et al 21 and Allner et al, 22 respectively. It should be noted that ff03 force-field parameters, which are identical to the ff99-SB 23 ones for nucleic acids, are able to reproduce the inorganic···organic interactions in biominerals, as was recently proved.…”

Electrostatics Explains the Position‐Dependent Effect of G⋅U Wobble Base Pairs on the Affinity of RNA Kissing Complexes

“…The complexes were neutralized with either only Na + ions or with am ixture of 30 Na + and 2Mg 2 + (magnesium parameters from Ref. [21]) and hydrated with TIP3P water molecules [22] in at runcated octahedron. The sodium-only simulations were run first.…”