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

Kara K Grotz,Nadine Schwierz

doi:10.1063/5.0087292

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 12 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.

Highlights

Molecular dynamics simulations rely on accurate force field parameters for biomolecules, water molecules, and ions
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
We calculated all physical properties that were targeted in the initial optimization including the solvation free energy, the distance to water oxygens in the first hydration shell, the hydration number, the activity coefficient derivative in MgCl2 solutions, and the binding affinity and distance to the non-bridging phosphate oxygens on nucleic acids

Summary

Introduction

Molecular dynamics simulations rely on accurate force field parameters for biomolecules, water molecules, and ions. It seems tempting to combine the force fields of the most promising water models with the most successful ion force fields in order to utilize the strengths of each parameter set. Even for simple cations, the transferability of the ion parameters to different water models is limited. It is crucial to assess whether the transfer of ion parameters to a different water model yields physically meaningful results. The aim of this work is to determine parameters for Mg2+ in OPC water that leverage the strengths of both force fields, reproduce a broad range of experimental properties, and lead to accurate simulation results of biomolecular systems

Objectives

Methods

Results

Conclusion