Optimized magnesium force field parameters for biomolecular simulations with accurate solvation, ion-binding, and water-exchange properties in SPC/E, TIP3P-fb, TIP4P/2005, TIP4P-Ew, and TIP4P-D

[Image: see text] Magnesium is essential in many vital processes. To correctly describe Mg(2+) in physiological processes by molecular dynamics simulations, accurate force fields are fundamental. Despite the importance, force fields based on the commonly used 12-6 Lennard-Jones potential showed significant shortcomings. Recently progress was made by an optimization procedure that implicitly accounts for polarizability. The resulting microMg and nanoMg force fields (J. Chem. Theory Comput.2021, 17, 2530–2540) accurately reproduce a broad range of experimental solution properties and the binding affinity to nucleic acids in TIP3P water. Since countless simulation studies rely on available water models and ion force fields, we here extend the optimization and provide Mg(2+) parameters in combination with the SPC/E, TIP3P-fb, TIP4P/2005, TIP4P-Ew, and TIP4P-D water models. For each water model, the Mg(2+) force fields reproduce the solvation free energy, the distance to oxygens in the first hydration shell, the hydration number, the activity coefficient derivative in MgCl(2) solutions, and the binding affinity and distance to the phosphate oxygens on nucleic acids. We present two parameter sets: MicroMg yields water exchange on the microsecond time scale and matches the experimental exchange rate. Depending on the water model, nanoMg yields accelerated water exchange in the range of 10(6) to 10(8) exchanges per second. The nanoMg parameters can be used to enhance the sampling of binding events, to obtain converged distributions of Mg(2+), or to predict ion binding sites in biomolecular simulations. The parameter files are freely available at https://github.com/bio-phys/optimizedMgFFs

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

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

Extended magnesium and calcium force field parameters for accurate ion–nucleic acid interactions in biomolecular simulations

Magnesium and calcium play an essential role in the folding and function of nucleic acids. To correctly describe their interactions with DNA and RNA in biomolecular simulations, an accurate parameterization is crucial. In most cases, the ion parameters are optimized based on a set of experimental solution properties such as solvation free energies, radial distribution functions, water exchange rates, and activity coefficient derivatives. However, the transferability of such bulk-optimized ion parameters to quantitatively describe biomolecular systems is limited. Here, we extend the applicability of our previous bulk-optimized parameters by including experimental binding affinities toward the phosphate oxygen on nucleic acids. In particular, we systematically adjust the combination rules that are an integral part of the pairwise interaction potentials of classical force fields. This allows us to quantitatively describe specific ion binding to nucleic acids without changing the solution properties in the most simple and efficient way. We show the advancement of the optimized Lorentz combination rule for two representative nucleic acid systems. For double-stranded DNA, the optimized combination rule for Ca2+>/sup> significantly improves the agreement with experiments, while the standard combination rule leads to unrealistically distorted DNA structures. For the add A-riboswitch, the optimized combination rule for Mg2+>/sup> improves the structure of two specifically bound Mg2+>/sup> ions as judged by the experimental distance to the binding site. Including experimental binding affinities toward specific ion binding sites on biomolecules, therefore, provides a promising perspective to develop a more accurate description of metal cations for biomolecular simulations

Optimized magnesium force field parameters for biomolecular simulations with accurate solvation, ion-binding, and water-exchange properties

Magnesium ions play an essential role in many vital processes. To correctly describe their interactions in molecular dynamics simulations, an accurate parametrization is crucial. Despite the importance and considerable scientific effort, current force fields based on the commonly used 12-6 Lennard-Jones interaction potential fail to reproduce a variety of experimental solution properties. In particular, no parametrization exists so far that simultaneously reproduces the solvation free energy and the distance to the water oxygens in the first hydration shell. Moreover, current Mg2+ force fields significantly underestimate the rate of water exchange leading to unrealistically slow exchange kinetics. In order to make progress in the development of improved models, we systematically optimize the Mg2+ parameters in combination with the TIP3P water model in a much larger parameter space than previously done. The results show that a long-ranged interaction potential and modified Lorentz-Berthelot combination rules allow us to accurately reproduce multiple experimental properties including the solvation free energy, the distances to the oxygens of the first hydration shell, the hydration number, the activity coefficient derivative in MgCl2 solutions, the self-diffusion coefficient, and the binding affinity to the phosphate oxygen of RNA. Matching this broad range of thermodynamic properties, we present two sets of optimal parameters: MicroMg yields water exchange on the microsecond timescale in agreement with experiments. NanoMg yields water exchange on the nanosecond timescale facilitating the direct observation of ion-binding events. As shown for the example of the add A-riboswitch, the optimized parameters correctly reproduce the structure of specifically bound ions and permit the de novo prediction of Mg2+-binding sites in biomolecular simulations

MeV neutrinos in double beta decay

The effect of Majorana neutrinos in the MeV mass range on the double beta decay of various isotopes is studied on pure phenomenological arguments. By using only experimental half life data, limits on the mixing parameter $U_{eh}^2$ of the order 10$^{-7}$ can be derived. Also the possible achievements of upcoming experiments and some consequences are outlined.Comment: 7 pages, 6 uudecoded EPS-figure

Overlap of QRPA states based on ground states of different nuclei --mathematical properties and test calculations--

The overlap of the excited states in quasiparticle random-phase approximation (QRPA) is calculated in order to simulate the overlap of the intermediate nuclear states of the double-beta decay. Our basic idea is to use the like-particle QRPA with the aid of the closure approximation and calculate the overlap as rigorously as possible by making use of the explicit equation of the QRPA ground state. The formulation is shown in detail, and the mathematical properties of the overlap matrix are investigated. Two test calculations are performed for relatively light nuclei with the Skyrme and volume delta-pairing energy functionals. The validity of the truncations used in the calculation is examined and confirmed.Comment: 17 pages, 15 figures, full paper following arXiv:1205.5354 and Phys. Rev. C 86 (2012) 021301(R

ML-based PBCH symbol detection and equalization for 5G Non-Terrestrial Networks

This paper delves into the application of Machine Learning (ML) techniques in the realm of 5G Non-Terrestrial Networks (5G-NTN), particularly focusing on symbol detection and equalization for the Physical Broadcast Channel (PBCH). As 5G-NTN gains prominence within the 3GPP ecosystem, ML offers significant potential to enhance wireless communication performance. To investigate these possibilities, we present ML-based models trained with both synthetic and real data from a real 5G over-the-satellite testbed. Our analysis includes examining the performance of these models under various Signal-to-Noise Ratio (SNR) scenarios and evaluating their effectiveness in symbol enhancement and channel equalization tasks. The results highlight the ML performance in controlled settings and their adaptability to real-world challenges, shedding light on the potential benefits of the application of ML in 5G-NTN

New Leptoquark Mechanism of Neutrinoless Double Beta Decay

A new mechanism for neutrinoless double beta (\znbb) decay based on leptoquark exchange is discussed. Due to the specific helicity structure of the effective four-fermion interaction this contribution is strongly enhanced compared to the well-known mass mechanism of \znbb decay. As a result the corresponding leptoquark parameters are severely constrained from non-observation of \znbb-decay. These constraints are more stringent than those derived from other experiments.Comment: LaTeX, 6 pages, 1 figur

Global Hopf bifurcation in the ZIP regulatory system

Regulation of zinc uptake in roots of Arabidopsis thaliana has recently been modeled by a system of ordinary differential equations based on the uptake of zinc, expression of a transporter protein and the interaction between an activator and inhibitor. For certain parameter choices the steady state of this model becomes unstable upon variation in the external zinc concentration. Numerical results show periodic orbits emerging between two critical values of the external zinc concentration. Here we show the existence of a global Hopf bifurcation with a continuous family of stable periodic orbits between two Hopf bifurcation points. The stability of the orbits in a neighborhood of the bifurcation points is analyzed by deriving the normal form, while the stability of the orbits in the global continuation is shown by calculation of the Floquet multipliers. From a biological point of view, stable periodic orbits lead to potentially toxic zinc peaks in plant cells. Buffering is believed to be an efficient way to deal with strong transient variations in zinc supply. We extend the model by a buffer reaction and analyze the stability of the steady state in dependence of the properties of this reaction. We find that a large enough equilibrium constant of the buffering reaction stabilizes the steady state and prevents the development of oscillations. Hence, our results suggest that buffering has a key role in the dynamics of zinc homeostasis in plant cells.Comment: 22 pages, 5 figures, uses svjour3.cl

R-parity Conserving Supersymmetry, Neutrino Mass and Neutrinoless Double Beta Decay

We consider contributions of R-parity conserving softly broken supersymmetry (SUSY) to neutrinoless double beta (\znbb) decay via the (B-L)-violating sneutrino mass term. The latter is a generic ingredient of any weak-scale SUSY model with a Majorana neutrino mass. The new R-parity conserving SUSY contributions to \znbb are realized at the level of box diagrams. We derive the effective Lagrangian describing the SUSY-box mechanism of \znbb-decay and the corresponding nuclear matrix elements. The 1-loop sneutrino contribution to the Majorana neutrino mass is also derived. Given the data on the \znbb-decay half-life of $^{76}$Ge and the neutrino mass we obtain constraints on the (B-L)-violating sneutrino mass. These constraints leave room for accelerator searches for certain manifestations of the 2nd and 3rd generation (B-L)-violating sneutrino mass term, but are most probably too tight for first generation (B-L)-violating sneutrino masses to be searched for directly.Comment: LATEX, 29 pages + 4 (uuencoded) figures appende