Magnesium force fields for OPC water with accurate solvation, ion-binding, and water-exchange properties: Successful transfer from SPC/E

Abstract

Magnesium plays a vital role in a large variety of biological processes. To model such processes by molecular dynamics simulations, researchers rely on accurate force field parameters for Mg2+ and water. OPC is one of the most promising water models yielding an improved description of biomolecules in water. The aim of this work is to provide force field parameters for Mg2+ that lead to accurate simulation results in combination with OPC water. Using twelve different Mg2+ parameter sets, that were previously optimized with different water models, we systematically assess the transferability to OPC based on a large variety of experimental properties. The results show that the Mg2+ parameters for SPC/E are transferable to OPC and closely reproduce the experimental solvation free energy, radius of the first hydration shell, coordination number, activity derivative, and binding affinity toward the phosphate oxygens on RNA. Two optimal parameter sets are presented: MicroMg yields water exchange in OPC on the microsecond timescale in agreement with experiments. NanoMg yields accelerated exchange on the nanosecond timescale and facilitates the direct observation of ion binding events for enhanced sampling purposes.

Trans-palmitoleic acid, a dairy fat biomarker, stimulates insulin secretion and activates G protein-coupled receptors with a different mechanism from the cis isomer

“…All preparation steps, simulations and trajectory postprocessing were performed using AMBER20 software. 36 Complexes obtained through molecular docking were subjected to preparation using tLeap, where ff19SB, 37 OPC, 38 lipid17, 39 and gaff2 40 force fields were defined for protein, water, lipid membrane, and ligands, respectively. Partial charges of ligands were calculated at the RESP 41,42 level of theory and inputs were generated using an antechamber.…”

RNA Captures More Cations than DNA: Insights from Molecular Dynamics Simulations

“…First, the simulations rely on accurate force fields for the nucleic acids, water, and ions. In particular, the force fields for the metal cations must be optimized to reproduce experimental solution properties , and ion binding affinities − in order to resolve the subtle differences between different cations. The second challenge for simulations is that for cation binding, the transition from a water-mediated outer-sphere to a direct inner-sphere coordination is on the micro- to millisecond time scale for metal cations with high charge density such as Mg 2+ . ,− Therefore, simulating an equilibrated distribution for highly charged ions is out of reach for conventional simulation techniques, and enhanced sampling schemes need to be applied. ,, Here, the quantitative comparison of experiments, simulations, and theoretical modeling is essential to drive the continuous improvement of atomistic models and theoretical methods. ,− In turn, simulations can contribute significantly to a deeper understanding of the interactions between cations and nucleic acids and reveal the selectivity of cation binding sites, , the sequence dependence of ion binding affinities, the influence of the handedness, or ion competition. − …”

“…First, the simulations rely on accurate force fields for the nucleic acids, water, and ions. In particular, the force fields for the metal cations must be optimized to reproduce experimental solution properties 30 , 31 and ion binding affinities 32 − 36 in order to resolve the subtle differences between different cations. The second challenge for simulations is that for cation binding, the transition from a water-mediated outer-sphere to a direct inner-sphere coordination is on the micro- to millisecond time scale for metal cations with high charge density such as Mg 2+ .…”

Structural Insights on Ionizable Dlin-MC3-DMA Lipids in DOPC Layers by Combining Accurate Atomistic Force Fields, Molecular Dynamics Simulations and Neutron Reflectivity

“…For instance, the Lipid17 force field can be combined easily with the AMBER force fields for proteins, small molecules, nucleic acids, and carbohydrates, which greatly enhances its use in the field of biomolecular simulations. Despite the consistent parameterization within one family, we may note that it is still recommended to carefully check whether such combinations lead to physically meaningful results for the system under consideration 12,13 .…”