Differential Stability Research Articles

The Glycosaminoglycan Side Chains and Modular Core Proteins of Heparan Sulphate Proteoglycans and the Varied Ways They Provide Tissue Protection by Regulating Physiological Processes and Cellular Behaviour.

This review examines the roles of HS-proteoglycans (HS-PGs) in general, and, in particular, perlecan and syndecan as representative examples and their interactive ligands, which regulate physiological processes and cellular behavior in health and disease. HS-PGs are essential for the functional properties of tissues both in development and in the extracellular matrix (ECM) remodeling that occurs in response to trauma or disease. HS-PGs interact with a biodiverse range of chemokines, chemokine receptors, protease inhibitors, and growth factors in immune regulation, inflammation, ECM stabilization, and tissue protection. Some cell regulatory proteoglycan receptors are dually modified hybrid HS/CS proteoglycans (betaglycan, CD47). Neurexins provide synaptic stabilization, plasticity, and specificity of interaction, promoting neurotransduction, neurogenesis, and differentiation. Ternary complexes of glypican-1 and Robbo-Slit neuroregulatory proteins direct axonogenesis and neural network formation. Specific neurexin-neuroligin complexes stabilize synaptic interactions and neural activity. Disruption in these interactions leads to neurological deficits in disorders of functional cognitive decline. Interactions with HS-PGs also promote or inhibit tumor development. Thus, HS-PGs have complex and diverse regulatory roles in the physiological processes that regulate cellular behavior and the functional properties of normal and pathological tissues. Specialized HS-PGs, such as the neurexins, pikachurin, and Eyes-shut, provide synaptic stabilization and specificity of neural transduction and also stabilize the axenome primary cilium of phototoreceptors and ribbon synapse interactions with bipolar neurons of retinal neural networks, which are essential in ocular vision. Pikachurin and Eyes-Shut interactions with an α-dystroglycan stabilize the photoreceptor synapse. Novel regulatory roles for HS-PGs controlling cell behavior and tissue function are expected to continue to be uncovered in this fascinating class of proteoglycan.

Kinetic Behavior and Optimal Control of a Fractional-Order Hepatitis B Model

The fractional-order calculus model is suitable for describing real-world problems that contain non-local effects and have memory genetic effects. Based on the definition of the Caputo derivative, the article proposes a class of fractional hepatitis B epidemic model with a general incidence rate. Firstly, the existence, uniqueness, positivity and boundedness of model solutions, basic reproduction number, equilibrium points, and local stability of equilibrium points are studied employing fractional differential equation theory, stability theory, and infectious disease dynamics theory. Secondly, the fractional necessary optimality conditions for fractional optimal control problems are derived by applying the Pontryagin maximum principle. Finally, the optimization simulation results of fractional optimal control problem are discussed. To control the spread of the hepatitis B virus, three control variables (isolation, treatment, and vaccination) are applied, and the optimal control theory is used to formulate the optimal control strategy. Specifically, by isolating infected and non-infected people, treating patients, and vaccinating susceptible people at the same time, the number of hepatitis B patients can be minimized, the number of recovered people can be increased, and the purpose of ultimately eliminating the transmission of hepatitis B virus can be achieved.

Where and when to start: Regulating DNA replication origin activity in eukaryotic genomes

ABSTRACT In eukaryotic genomes, hundreds to thousands of potential start sites of DNA replication named origins are dispersed across each of the linear chromosomes. During S-phase, only a subset of origins is selected in a stochastic manner to assemble bidirectional replication forks and initiate DNA synthesis. Despite substantial progress in our understanding of this complex process, a comprehensive ‘identity code’ that defines origins based on specific nucleotide sequences, DNA structural features, the local chromatin environment, or 3D genome architecture is still missing. In this article, we review the genetic and epigenetic features of replication origins in yeast and metazoan chromosomes and highlight recent insights into how this flexibility in origin usage contributes to nuclear organization, cell growth, differentiation, and genome stability.

High-throughput thermal denaturation of tryptophanyl-tRNA synthetase combinatorial mutants reveals high-order energetic coupling determinants of conformational stability.

Landscape descriptions provide a framework for identifying functionally significant dynamic linkages in proteins but cannot supply details. Rate measurements of combinatorial mutations can implicate dynamic linkages in catalysis. A major difficulty is filtering dynamic linkages from the vastly more numerous static interactions that stabilize domain folding. The Geobacillus stearothermophilus (TrpRS) D1 switch is such a dynamic packing motif; it links domain movement to catalysis and specificity. We describe Thermofluor and far UV circular dichroism melting curves for all 16 D1 switch variants to determine their higher-order impact on unliganded TrpRS stability. A prominent transition at intermediate temperatures in TrpRS thermal denaturation is molten globule formation. Combinatorial analysis of thermal melting transcends the protein landscape in four significant respects: (i) bioinformatic methods identify dynamic linkages from coordinates of multiple conformational states. (ii) Relative mutant melting temperatures, δTM, are proportional to free energy changes. (iii) Structural analysis of thermal melting implicates unexpected coupling between the D1 switch packing and regions of high local frustration. Those segments develop molten globular characteristics at the point of greatest complementarity to the chemical transition state and are the first TrpRS structures to melt. (iv) Residue F37 stabilizes both native and molten globular states; its higher-order interactions modify the relative intrinsic impacts of mutations to other D1 switch residues from those estimated for single point mutants. The D1 switch is a central component of an escapement mechanism essential to free energy transduction. These conclusions begin to relate the escapement mechanism to differential TrpRS conformational stabilities.

Genetic Diversity in Original Arabian-WAHO, Local and Thoroughbred Horses in Iraq from ACTN3-EXON19 Gene Polymorphism

The research was conducted in the Iraqi Equestrian Club (15 km west of Baghdad city center) for the period from 10/1/2021 to 11/30/2022, with the aim of detecting genetic features in the ACTN3 gene for each of the nineteenth exon (EXON19) in three types of horses, which are the original Arabian-WAHO, Local, and British Thoroughbred, with 38, 38, and 39 head each, respectively, for the purpose of studying genetic diversity indicators by estimating Mean allelic abundance -na) and some fixation indexes. The average total allelic abundance (na) for all mutation sites in the ACTN3/EXON19 gene for the three types of horses was 2.00, while the total number of effective alleles (ne) was 1.437, 1.594 and 1.592 for original Arabian-WAHO, Local, and British Thoroughbred respectively. The individual (Fis) for all mutation sites in the ACTN3 gene within the horse herd and for each type of them - 0.113, -0.107, and -0.138 for original Arabian-WAHO, Local, and the British Thoroughbred horses respectively, with a total rate of -0.1197, and that most of the estimates of genetic similarity between mutation sites in the ACTN3 gene are medium to high. We can conclude by studying the genetic diversity according to the genetic manifestations in the ACTN3 gene for each of the nineteenth exon EXON19, the possibility of adopting it in developing strategies for genetic improvement in horses and that the herd is characterized by the lack of internal breeding, and by studying the genetic differentiation stability index (Fst) and gene flow (Nm), there is genetic diversity in the studied gene regions, and the ACTN3 gene can be considered as a marker or genetic marker.

Differential Metabolic Stability of 4α,25- and 4β,25-Dihydroxyvitamin D3 and Identification of Their Metabolites.

Vitamin D3 (1) is metabolized by various cytochrome P450 (CYP) enzymes, resulting in the formation of diverse metabolites. Among them, 4α,25-dihydroxyvitamin D3 (6a) and 4β,25-dihydroxyvitamin D3 (6b) are both produced from 25-hydroxyvitamin D3 (2) by CYP3A4. However, 6b is detectable in serum, whereas 6a is not. We hypothesized that the reason for this is a difference in the susceptibility of 6a and 6b to CYP24A1-mediated metabolism. Here, we synthesized 6a and 6b, and confirmed that 6b has greater metabolic stability than 6a. We also identified 4α,24R,25- and 4β,24R,25-trihydroxyvitamin D3 (16a and 16b) as metabolites of 6a and 6b, respectively, by HPLC comparison with synthesized authentic samples. Docking studies suggest that the β-hydroxy group at C4 contributes to the greater metabolic stability of 6b by blocking a crucial hydrogen-bonding interaction between the C25 hydroxy group and Leu325 of CYP24A1.

One kilometer balanced analog photonic link based on a single multicore fiber

A one kilometer balanced microwave photonic link based on a single four core multicore optical fiber is demonstrated for the first time, to the best of our knowledge. The radio frequency gains and differential phase stabilities over temperature were measured and compared to a conventional balanced link based on two spans of single mode fiber. Both the multicore fiber link and the single mode fiber balanced link exhibited differential phase fluctuations of |Δφ|≤13° at 25 GHz (corresponding to a differential delay or skew, |Δt|, of ≤1.4ps) under identical periodic temperature oscillations of ±13°C over a 60 min period. In contrast, previous studies have shown that two single mode fiber spans should have exhibited up to an order of magnitude greater Δφs compared to the multicore fiber. Our different results can be attributed to how the fibers are arranged; the previous works kept the two single mode fiber spans separate, on different spools, whereas in this work the two single mode fiber spans were co-located as close as possible together by spooling them ‘side-by-side’ onto a single mandrel, more representative of a balanced link in application. In addition, the radio-frequency crosstalk between the multicore fiber’s cores were measured, exhibiting acceptable levels at least 60 dB below the signal for all core combinations. The crosstalk is shown to be dominated by occurrences at localized points, e.g. at the multiplexers (fan-in/fan-outs) and splices, rather than during propagation. Regardless of the single mode fiber link’s performance, the measurements here demonstrate that multicore fiber-based balanced links are a viable single fiber alternative to conventional dual single mode fiber-based balanced links.

Dynamical behaviour of an intraguild predator–prey model with prey refuge and hunting cooperation

ABSTRACT An intraguild predator–prey model including prey refuge and hunting cooperation is investigated in this paper. First, for the corresponding ordinary differential equation model, the existence and stability of all equilibria are given, and the existence of Hopf bifurcation, direction and stability of bifurcating periodic solutions are investigated. Then, for partial differential equation model, the diffusion-driven Turing instability is obtained. What is more, the existence and non-existence of the non-constant positive steady state of the reaction–diffusion model are established by the Leray–Schauder degree theory and some priori estimates. Next, some numerical simulations are performed to support analytical results. The results showed that prey refuge can change the stability of model and even have a stabilizing effect on this model, meanwhile the hunting cooperation can make such model without diffusion unstable, but make such model with diffusion stable. Lastly, a brief conclusion is concluded in the last section.

Energy management strategy of field power station based on differential hysteresis voltage stabilization

The existing field power stations mainly use diesel generator sets for power supply, with poor power supply stability and no uninterrupted power supply capability. Therefore, a hybrid energy storage device is introduced into the field power station to improve it. According to the working characteristics of different energy sources, an energy management strategy based on differential hysteresis voltage stabilization is proposed. Hysteresis voltage stabilization control makes it true that the diesel generator set as the main energy source works for a long time, and the battery as a backup energy source works when necessary. Differential voltage stabilization control realizes coordination control of the two, which allows the battery to exit work smoothly. The strategy can get transient stability and stable economy, and extend the life of the battery. Simulation results show that this strategy is superior to the traditional hysteresis voltage stabilization strategy.

Comparative structural study of selective and non-selective NSAIDs against the enzyme cyclooxygenase-2 through real-time molecular dynamics linked to post-dynamics MM-GBSA and e-pharmacophores mapping.

Inflammation-provoked disorders including cancer are arbitrated by cyclooxygenase-2 (COX-2). Celecoxib and niflumic acid are amongthe potent and selective inhibitors of this enzyme while aspirin (acetylsalicylic acid) and sodium salicylate are its non-selective and lesser potent inhibitors. Despite these proven studies, the comparative structural study of these selective and non-selective molecules at atomistic scale in complex state with COX-2 that may answer this differential inhibitory behavior has not been accomplished spotlighting the imperative need of additional research in this area. Thus, this study was framed to provide a strong explanation for the enigma of higher inhibitory activity of celecoxib-niflumic acid duo in comparison to aspirin and sodium salicylate towards COX-2. A contemporary approach including advanced molecular docking against COX2, molecular dynamics of receptor-ligand complexes, simulation-trajectory-backed MMGBSA for different time points, radius of gyration (Rg) calculations, and e-pharmacophores approach was employed to attain a rational conclusion. Our findings demonstrated the higher binding affinity of celecoxib and niflumic acid over aspirin and sodium salicylate against COX-2. Although both selective and non-selective COX-2 inhibitors manifested nearly the same stability in the active site of this enzyme but the e-pharmocophoric features found in the case of selective inhibitors scored over non-selective ones. Thus, our findings excluded the differential stability to be the cause of stronger potency of selective inhibitors but attributed their potency to greater number of complementary features present in these inhibitors against the active site of inflammation engendering COX-2.

Carbon sequestration potential and fractionation in soils after conversion of cultivated land to hedgerows

Hedgerows supply multiple ecosystem services in agricultural landscapes and have been advocated to provide a relevant carbon sink for climate change mitigation. Using a space-for-time approach, we investigated carbon sequestration and fractionation in soils beneath hedgerows 1 to 70 yr after planting on cultivated land in the humid continental climate of Eastern Austria. We sampled 54 pairs of hedgerow and adjacent cultivated soil volumetrically to 40 cm depth and analysed them for bulk soil (< 2 mm) mass, SOC fractions of differential stability and related soil properties. Total SOC stocks to 40 cm depth increased significantly (p < 0.05) by 34.7 ± 4.70 Mg C ha−1 to 119 ± 6.77 Mg C ha−1 beneath 31–70 yr old hedgerows, and by 15.6 ± 5.94 Mg C ha−1 to 106 ± 8.98 Mg C ha−1 beneath 1–30 yr old hedgerows. Carbon sequestration was limited to the organic and mineral topsoil layer (0–20 cm), SOC changes (ΔSOC) at 20–40 cm depth were small and insignificant (p < 0.05). Linear regression of ΔSOC on hedgerow age (1–70 yr) yields a mean SOC sequestration rate of 0.65 ± 0.10 Mg ha−1 yr−1 down to 40 cm depth. Combining our data with published work we found hedgerow age explaining ∼65 % of the variation of ΔSOC in topsoils, and ∼68 % in shallow subsoils; ΔSOC increases with hedgerow age in topsoils, but declines in subsoils. Annual sequestration rates decline with hedgerow age in both soil layers. Up to 30 years after conversion, SOC is preferably sequestered in labile particulate organic matter (POM; > 20 µm), and stabilised in the mineral-associated organic matter (MAOM; < 20 µm fraction) thereafter. In the bulk soil and MAOM fraction, SOC strongly increases with oxalate-extractable Al (Alo). We conclude that SOC sequestration beneath hedgerows offers a relevant CO2 sequestration potential which is mainly limited to topsoils and primarily controlled by hedgerow age and Alo.

Application of Sucrose Acetate Isobutyrate in Development of Co-Amorphous Formulations of Tacrolimus for Bioavailability Enhancement.

The focus of the present work was to develop co-amorphous dispersion (CAD) formulations of tacrolimus (TAC) using sucrose acetate isobutyrate as a carrier, evaluate by in vitro and in vivo methods and compare its performance with hydroxypropyl methylcellulose (HPMC) based amorphous solid dispersion (ASD) formulation. CAD and ASD formulations were prepared by solvent evaporation method followed by characterization by Fourier transformed infrared spectroscopy, X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), dissolution, stability, and pharmacokinetics. XRPD and DSC indicated amorphous phase transformation of the drug in the CAD and ASD formulations, and dissolved more than 85% of the drug in 90 min. No drug crystallization was observed in the thermogram and diffractogram of the formulations after storage at 25 °C/60% RH and 40 °C/75% RH. No significant change in the dissolution profile was observed after and before storage. SAIB-based CAD and HPMC-based ASD formulations were bioequivalent as they met 90% confidence of 90-11.1% for Cmax and AUC. The CAD and ASD formulations exhibited Cmax and AUC 1.7-1.8 and 1.5-1.8 folds of tablet formulations containing the drug's crystalline phase. In conclusion, the stability, dissolution, and pharmacokinetic performance of SAIB-based CAD and HPMC-based ASD formulations were similar, and thus clinical performance would be similar.

Dual domain recognition determines SARS-CoV-2 PLpro selectivity for human ISG15 and K48-linked di-ubiquitin

The Papain-like protease (PLpro) is a domain of a multi-functional, non-structural protein 3 of coronaviruses. PLpro cleaves viral polyproteins and posttranslational conjugates with poly-ubiquitin and protective ISG15, composed of two ubiquitin-like (UBL) domains. Across coronaviruses, PLpro showed divergent selectivity for recognition and cleavage of posttranslational conjugates despite sequence conservation. We show that SARS-CoV-2 PLpro binds human ISG15 and K48-linked di-ubiquitin (K48-Ub2) with nanomolar affinity and detect alternate weaker-binding modes. Crystal structures of untethered PLpro complexes with ISG15 and K48-Ub2 combined with solution NMR and cross-linking mass spectrometry revealed how the two domains of ISG15 or K48-Ub2 are differently utilized in interactions with PLpro. Analysis of protein interface energetics predicted differential binding stabilities of the two UBL/Ub domains that were validated experimentally. We emphasize how substrate recognition can be tuned to cleave specifically ISG15 or K48-Ub2 modifications while retaining capacity to cleave mono-Ub conjugates. These results highlight alternative druggable surfaces that would inhibit PLpro function.

Enabling Molecular-Level Computational Description of Redox and Proton-Coupled Electron Transfer Reactions of Samarium Diiodide.

Samarium diiodide (SmI2, Kagan's reagent) is a one-electron reductant with applications ranging from organic synthesis to nitrogen fixation. Highly inaccurate relative energies of redox and proton-coupled electron transfer (PCET) reactions of Kagan's reagent are predicted by pure and hybrid density functional approximations (DFAs) when only scalar relativistic effects are accounted for. Calculations including spin-orbit coupling (SOC) show that the SOC-induced differential stabilization of the Sm(III) versus the Sm(II) ground state is little affected by ligands and solvent, and a standard SOC correction derived from atomic energy levels is thus included in the reported relative energies. With this correction, selected meta-GGA and hybrid meta-GGA functionals predict Sm(III)/Sm(II) reduction free energies to within 5 kcal/mol of the experiment. Considerable discrepancies remain, however, in particular for the PCET-relevant O-H bond dissociation free energies, for which no regular DFA is within 10 kcal/mol of the experiment or CCSD(T). The main cause behind these discrepancies is the delocalization error, which leads to excess ligand-to-metal electron donation and destabilizes Sm(III) versus Sm(II). Fortunately, static correlation is unimportant for the present systems, and the error may be reduced by including information from virtual orbitals via perturbation theory. Contemporary, parametrized double-hybrid methods offer promise as companions to experimental campaigns in the further development of the chemistry of Kagan's reagent.

Transcription of MERVL retrotransposons is required for preimplantation embryo development

Zygotic genome activation (ZGA) is a critical postfertilization step that promotes totipotency and allows different cell fates to emerge in the developing embryo. MERVL (murine endogenous retrovirus-L) is transiently upregulated at the two-cell stage during ZGA. Although MERVL expression is widely used as a marker of totipotency, the role of this retrotransposon in mouse embryogenesis remains elusive. Here, we show that full-length MERVL transcripts, but not encoded retroviral proteins, are essential for accurate regulation of the host transcriptome and chromatin state during preimplantation development. Both knockdown and CRISPRi-based repression of MERVL result in embryonic lethality due to defects in differentiation and genomic stability. Furthermore, transcriptome and epigenome analysis revealed that loss of MERVL transcripts led to retention of an accessible chromatin state at, and aberrant expression of, a subset of two-cell-specific genes. Taken together, our results suggest a model in which an endogenous retrovirus plays a key role in regulating host cell fate potential.

Dynamic Modeling and Simulation of Integrated Electricity and Gas Systems

The dynamic simulation of the integrated electricity and gas system (IEGS) is effective for accurate operational guidance. However, the IEGS model governed by partial and ordinary differential-algebraic equations (PDAE) is challenging for analysis, because it poses heterogeneous properties, high dimensionality, and strong nonlinearity. To eliminate the nonlinear terms, this paper firstly derives the expression of average flow velocity (AFV) and reformulates the gas flow dynamics into the variable-coefficient partial differential equations (VC-PDE), whose consistency, stability, and convergence can be theoretically guaranteed. Then, a novel adaptive step size control (ASC) strategy is developed for VC-PDE solvers to improve computational efficiency and accuracy. Finally, this paper builds a framework for the simulation of IEGS considering the dynamics in the natural gas network (NGN) and coupling units, where the bidirectional interaction between the electric power system (EPS) and NGN is investigated. Case studies verify the superiority of the proposed VC-PDE solver with ASC regarding accuracy, stability, convergence, and efficiency in different systems.

Boundary Value Problems for Fractional Differential Equations of Caputo Type and Ulam Type Stability: Basic Concepts and Study

Boundary value problems are very applicable problems for different types of differential equations and stability of solutions, which are an important qualitative question in the theory of differential equations. There are various types of stability, one of which is the so called Ulam-type stability, and it is a special type of data dependence of solutions of differential equations. For boundary value problems, this type of stability requires some additional understanding, and, in connection with this, we discuss the Ulam-Hyers stability for different types of differential equations, such as ordinary differential equations and generalized proportional Caputo fractional differential equations. To propose an appropriate idea of Ulam-type stability, we consider a boundary condition with a parameter, and the value of the parameter depends on the chosen arbitrary solution of the corresponding differential inequality. Several examples are given to illustrate the theoretical considerations.

Comparative Analysis of Protein Folding Stability-Based Profiling Methods for Characterization of Biological Phenotypes.

Recently, a new suite of mass spectrometry-based proteomic methods has been developed that enables evaluation of protein folding stability on the proteomic scale. These methods utilize chemical and thermal denaturation approaches (SPROX and TPP, respectively) as well as proteolysis strategies (DARTS, LiP, and PP) to assess protein folding stability. The analytical capabilities of these technique have been well-established for protein target discovery applications. However, less is known about the relative advantages and disadvantages of using these different strategies to characterize biological phenotypes. Reported here is a comparative study of SPROX, TPP, LiP, and conventional protein expression level measurements using both a mouse model of aging and a mammalian cell culture model of breast cancer. Analyses on proteins in brain tissue cell lysates derived from 1- and 18-month-old mice (n = 4-5 at each time point) and on proteins in cell lysates derived from the MCF-7 and MCF-10A cell lines revealed a majority of the differentially stabilized protein hits in each phenotype analysis had unchanged expression levels. In both phenotype analyses, TPP generated the largest number and fraction of differentially stabilized protein hits. Only a quarter of all the protein hits identified in each phenotype analysis had a differential stability that was detected using multiple techniques. This work also reports the first peptide-level analysis of TPP data, which was required for the correct interpretation of the phenotype analyses performed here. Studies on selected protein stability hits also uncovered phenotype-related functional changes.

Mathematical modelling of COVID-19 pandemic in Pakistan with optimal control

We propose an innovative mathematical modeling to examine the previous coronavirus disease of 2019 pandemic or (COVID-19). This analysis has been performed qualitatively through differential equation stability theory, as well as the basic reproductive value, which indicates a pandemic index, then calculated from the maximum eigenvalue of the subsequent matrix. We establish the global asymptotic stability criteria for such disease-free state. The actual COVID-19 occurrence documents and data from 01 July, 2021 to 14 August, 2022 in Pakistan are analyzed for estimation methods, leading in fitted values for biological parameters. Sensitivity analyzation is used to identify the much more relevant attributes in the developed framework. This scientific research revealed a deterministic computational formula that assesses the impact of various mitigation measures on the propagation of COVID-19 in a worldwide population. The analysis will concentrate on Pakistan, and relevant data gathered out of that region. If the method were modified for the total number of COVID-19 reported patients as well as the total number of active patients in the Pakistan region, infection rates would be approximated fairly. This research will in some way give government authorities including local hospitals additional knowledge about how to enhance precautionary efforts to minimize infection propagation.

Improved polarizable force field for modeling Mg2+ binding to proteins and nucleotides.

Magnesium (Mg2+) is an indispensable regulatory cation for numerous cellular enzymes and membrane proteins that participate in a variety of biological processes, including cell signaling, glycolysis, cell differentiation, and genome stability. Molecular mechanics (MM) simulations have the potential to provide detailed insights into the mechanisms of these Mg-dependent proteins. However, MM force fields continue to suffer from large inaccuracies when dealing with divalent cations. The inclusion of explicit polarization in MM models, such as in CHARMM Drude and AMOEBA models, has been promising, but despite substantial improvements over non-polarizable models, errors in interactions of proteins with divalent cations remain in excess of 10 kcal/mol. Such errors are present even with ‘nonbonded-fix (NB-fix)’ corrections. Modeling becomes even more problematic when dealing with enzymes like kinases and phosphatases, where Mg2+ ions interact directly with both proteins and nucleotides. Toward addressing this long-standing challenge, we recently presented a recalibration of the AMOEBA model (Delgado et al. J Chem. Info. Model. 2022). Notably, polarization terms of cation-coordinating groups were improved to respond better to the high electric fields present near cations. This systematically reduced errors in interactions of monovalent cations with proteins. Here we show that this revised model, along with our many body NB-fix (MB-NB-fix) corrections, reduces errors in Mg2+-protein interaction energies to 5 kcal/mol. MB-NB-fix corrections also improve predictions of Mg2+-ATP interactions substantially. Errors are computed with respect to estimates from vdW-inclusive density functional theory that we benchmark against "gold standard" CCSD(T) calculations and experiments. We will also present the ramifications of these improvements in local interactions on Mg2+-ATP binding free energies and binding modes in bulk water, and on complexation of Mg2+ and ATP with proteins.