Modification Of Interaction Research Articles

Likely Overstabilization of Charge-Charge Interactions in CHARMM36m(w): A Case for a99SB-disp Water.

Recent years have witnessed drastic improvements in general-purpose explicit solvent protein force fields, partially driven by the need to study intrinsically disordered proteins (IDPs), and yet the state-of-the-art force fields such as CHARMM36m (c36m) and a99SB-disp still provide different performances in simulating disordered protein states, where c36m has a bias toward overcompaction for large IDPs. Here, we examine the performance of c36m and a99SB-disp in describing the stabilities of a set of 46 amino acid backbone and side chain pairs in various configurations. The free energy results show that c36m systematically predicts stronger interactions compared to a99SB-disp by an average of 0.2 kcal/mol for nonpolar pairs, 0.6 kcal/mol for polar pairs, and 0.8 kcal/mol for salt bridges. The most severe overstabilization in c36m is observed for charged pairs involving the Arg and Glu side chains by up to 2.9 kcal/mol. Importantly, the systematic overstabilization of c36m is only marginally alleviated by c36mw, an ad hoc patch to c36m that increases the dispersion interactions between TIP3P hydrogens and protein atoms. Guided by free energy decomposition, we evaluated if revising the charges alone could alleviate the severe overstabilization of salt bridges of c36m(w) vs a99SB-disp. The results suggested that the direct modification of protein-water interactions is also necessary. Toward this end, we proposed a tentative modification to c36m, referred to as c36mrb-disp, which combines modified Arg side chain charges, retuned backbone hydrogen bonding strength, and the a99SB-disp water model. The modified force field successfully reproduces the secondary structures of several intrinsically disordered peptides and proteins including (AAQAA)3, GB1p, and p53 transactivation domain, while maintaining the stability of a set of folded proteins. This work provides a set of useful systems for benchmarking and optimizing protein force fields and highlights the importance of balancing protein-protein and protein-water electrostatic interactions for accurately describing both folded and disordered proteins.

Cavity-modified local and non-local electronic interactions in molecular ensembles under vibrational strong coupling.

Resonant vibrational strong coupling (VSC) between molecular vibrations and quantized field modes of low-frequency optical cavities constitutes the conceptual cornerstone of vibro-polaritonic chemistry. In this work, we theoretically investigate the role of complementary nonresonant electron-photon interactions in the cavity Born-Oppenheimer (CBO) approximation. In particular, we study cavity-induced modifications of local and non-local electronic interactions in dipole-coupled molecular ensembles under VSC. Methodologically, we combine CBO perturbation theory (CBO-PT) [E. W. Fischer and P. Saalfrank, J. Chem. Theory Comput. 19, 7215 (2023)] with non-perturbative CBO Hartree-Fock (HF) and coupled cluster (CC) theories. In a first step, we derive up to second-order CBO-PT cavity potential energy surfaces, which reveal non-trivial intra- and inter-molecular corrections induced by the cavity. We then introduce the concept of a cavity reaction potential (CRP), minimizing the electronic energy in the cavity subspace to discuss vibro-polaritonic reaction mechanisms. We present reformulations of CBO-HF and CBO-CC approaches for CRPs and derive second-order approximate CRPs from CBO-PT for unimolecular and bimolecular scenarios. In the unimolecular case, we find small local modifications of molecular potential energy surfaces for selected isomerization reactions dominantly captured by the first-order dipole fluctuation correction. Excellent agreement between CBO-PT and non-perturbative wave function results indicates minor VSC-induced state relaxation effects in the single-molecule limit. In the bimolecular scenario, CBO-PT reveals an explicit coupling of interacting dimers to cavity modes besides cavity-polarization dependent dipole-induced dipole and van der Waals interactions with enhanced long-range character. An illustrative CBO-coupled cluster theory with singles and doubles-based numerical analysis of selected molecular dimer models provides a complementary non-perturbative perspective on cavity-modified intermolecular interactions under VSC.

The Neural Correlations of Olfactory Associative Reward Memories in Drosophila.

Advancing treatment to resolve human cognitive disorders requires a comprehensive understanding of the molecular signaling pathways underlying learning and memory. While most organ systems evolved to maintain homeostasis, the brain developed the capacity to perceive and adapt to environmental stimuli through the continuous modification of interactions within a gene network functioning within a broader neural network. This distinctive characteristic enables significant neural plasticity, but complicates experimental investigations. A thorough examination of the mechanisms underlying behavioral plasticity must integrate multiple levels of biological organization, encompassing genetic pathways within individual neurons, interactions among neural networks providing feedback on gene expression, and observable phenotypic behaviors. Model organisms, such as Drosophila melanogaster, which possess more simple and manipulable nervous systems and genomes than mammals, facilitate such investigations. The evolutionary conservation of behavioral phenotypes and the associated genetics and neural systems indicates that insights gained from flies are pertinent to understanding human cognition. Rather than providing a comprehensive review of the entire field of Drosophila memory research, we focus on olfactory associative reward memories and their related neural circuitry in fly brains, with the objective of elucidating the underlying neural mechanisms, thereby advancing our understanding of brain mechanisms linked to cognitive systems.

Symbiotic bacteria Sodalis glossinidius, Spiroplasma sp and Wolbachia do not favour Trypanosoma grayi coexistence in wild population of tsetse flies collected in Bobo-Dioulasso, Burkina Faso.

Tsetse flies, the biological vectors of African trypanosomes, have established symbiotic associations with different bacteria. Their vector competence is suggested to be affected by bacterial endosymbionts. The current study provided the prevalence of three tsetse symbiotic bacteria and trypanosomes in Glossina species from Burkina Faso. A total of 430 tsetse flies were captured using biconical traps in four different collection sites around Bobo-Dioulasso (Bama, Bana, Nasso, and Peni), and their guts were removed. Two hundred tsetse were randomly selected and their guts were screened byPCR for the presence of Sodalis glossinidius, Spiroplasmasp., Wolbachia and trypanosomes. Of the 200 tsetse, 196 (98.0%) were Glossina palpalis gambienseand 4 (2.0%) Glossina tachinoides. The overall symbiont prevalence was 49.0%, 96.5%, and 45.0%, respectively for S. glossinidius, Spiroplasma and Wolbachia. Prevalence varied between sampling locations: S. glossinidius(54.7%, 38.5%, 31.6%, 70.8%); Spiroplasma (100%, 100%, 87.7%, 100%); and Wolbachia(43.4%, 38.5%, 38.6%, 70.8%),respectively in Bama, Bana, Nasso and Peni. Noteworthy, no G. tachhnoideswas infected by S. glossinidius and Wolbachia, but they were all infected by Spiroplasma sp. A total of 196 (98.0 %) harbored at least one endosymbionts. Fifty-five (27.5%) carried single endosymbiont. Trypanosomes were found only in G.p. gambiense, but not G. tachinoides. Trypanosomes were present in flies from all study locations with an overall prevalence of 29.5%. In Bama, Bana, Nasso, and Peni, the trypanosome infection rate was respectively 39.6%, 23.1%, 8.8%, and 37.5%. Remarkably, only Trypanosoma grayi was present. Of all trypanosome-infected flies, 55.9%, 98.3%, and 33.9% hosted S. glossinidius, Spiroplasma sp and Wolbachia, respectively. There was no association between Sodalis, Spiroplasma and trypanosome presence, but there was a negative association with Wolbachia presence. We reported1.9 times likelihood of trypanosome absence when Wolbachia was present. This is the first survey reporting the presence of Trypanosoma grayi in tsetse from Burkina Faso. Tsetse from these localities were highly positive for symbiotic bacteria, more predominantly with Spiroplasma sp. Modifications of symbiotic interactions may pave way for disease control.

Epigenomic landscapes during prefrontal cortex development and aging in rhesus.

The prefrontal cortex (PFC) is essential for higher-level cognitive functions. How epigenetic dynamics participates in PFC development and aging is largely unknown. Here, we profiled epigenomic landscapes of rhesus monkey PFCs from prenatal to aging stages. The dynamics of chromatin states, including higher-order chromatin structure, chromatin interaction and histone modifications are coordinated to regulate stage-specific gene transcription, participating in distinct processes of neurodevelopment. Dramatic changes of epigenetic signals occur around the birth stage. Notably, genes involved in neuronal cell differentiation and layer specification are pre-configured by bivalent promoters. We identified a cis-regulatory module and the transcription factors (TFs) associated with basal radial glia development, which was associated with large brain size in primates. These TFs include GLI3, CREB5 and SOX9. Interestingly, the genes associated with the basal radial glia (bRG)-associated cis-element module, such as SRY and SOX9, are enriched in sex differentiation. Schizophrenia-associated single nucleotide polymorphisms are more enriched in super enhancers (SEs) than typical enhancers, suggesting that SEs play an important role in neural network wiring. A cis-regulatory element of DBN1 is identified, which is critical for neuronal cell proliferation and synaptic neuron differentiation. Notably, the loss of distal chromatin interaction and H3K27me3 signal are hallmarks of PFC aging, which are associated with abnormal expression of aging-related genes and transposon activation, respectively. Collectively, our findings shed light on epigenetic mechanisms underlying primate brain development and aging.

Unveiling the Role of Spin Currents on the Giant Rashba Splitting in Single-Layer WSe2.

The Rashba spin splitting in uniaxial, inversion-asymmetric materials has attracted considerable interest for spintronic applications. The most widely used theoretical framework to model such states is Kohn-Sham density functional theory (DFT) in combination with standard (semi)local exchange-correlation density functional approximations (DFAs). However, in the presence of spin-orbit coupling, DFT misses contributions due to modification of the many-body interaction by spin currents J⃗. Inclusion of the latter effects requires a spin current DFT (SCDFT) formulation, which is seldom considered. We investigate the giant Rashba splitting in single-layer WSe2, and we quantify the effect of including spin currents in DFAs of the SCDFT. Crucially, we show that SCDFT allows fully capturing the giant Rashba band splitting in single-layer WSe2, otherwise previously systematically underestimated by standard (semi)local DFAs within the DFT framework. We find the inclusion of J⃗ on the DFA increases the Rashba splitting by about 20%.

Exploring the impact of cresols on aggregation characteristics of non-linear PEO-PPO-PEO block copolymers in aqueous solution

The present research investigates the intricate interplay between some industrially essential compounds, viz. 2-methylphenol (o-cresol, OC), 4-methylphenol (p-cresol, PC), 4-n-Butylphenol (BP) and non-linear ethylene oxide-propylene oxide (EO-PO) type block copolymers (Tetronics®) in aqueous solutions by employing an array of physico-chemical techniques. Each examined Tetronic® possesses 40% EO segments in its molecular structure. The study delves into the interaction and structural modifications that occur when cresols are doped into the copolymer solutions. The added cresols disrupt the hydrophilic-hydrophobic balance of Tetronics® depending on their hydrophobicities. The lowering of the cloud point (CP) is accompanied by a corresponding increase in solution viscosity. Doping of OC and PC has a dissimilar effect on viscosity compared to BP. The intermicellar interactions are adjudged to be probable cause of the unusual viscosity trend. Scattering techniques (DLS and SANS) confirm the morphology of aggregates. The results are interpreted in terms of H-bonding.

Food web context modifies predator foraging and weakens trophic interaction strength.

Trophic interaction modifications (TIM) are widespread in natural systems and occur when a third species indirectly alters the strength of a trophic interaction. Past studies have focused on documenting the existence and magnitude of TIMs; however, the underlying processes and long-term consequences remain elusive. To address this gap, we experimentally quantified the density-dependent effect of a third species on a predator's functional response. We conducted short-term experiments with ciliate communities composed of a predator, prey and non-consumable 'modifier' species. In both communities, increasing modifier density weakened the trophic interaction strength, due to a negative effect on the predator's space clearance rate. Simulated long-term dynamics indicate quantitative differences between models that account for TIMs or include only pairwise interactions. Our study demonstrates that TIMs are important to understand and predict community dynamics and highlights the need to move beyond focal species pairs to understand the consequences of species interactions in communities.

Effect of Cobalt on the Microstructure of Fe-B-Sn Amorphous Metallic Alloys

Fe78B15Sn7 and (Fe3Co1)78B15Sn7 amorphous metallic alloys were prepared using the method of planar flow casting. The amorphous nature of ribbons containing 7 at. % Sn was verified by X-ray diffraction. The resulting chemical composition was checked by flame atomic absorption spectroscopy and by mass spectrometry with inductively coupled plasma. The microstructure of the as-quenched metallic glasses was investigated by 57-Fe and 119-Sn Mössbauer spectrometry. The experiments were performed with transmission geometry at 300 K, 100 K, and 4.2 K, and in an external magnetic field of 6 T. The replacement of a quarter of the Fe by Co did not cause significant modifications of the hyperfine interactions in the 57-Fe nuclei. The observed minor variations in the local magnetic microstructure were attributed to alterations in the topological short-range order. However, the in-field 57-Fe Mössbauer spectra indicated a misalignment of the partial magnetic moments. On the other hand, the presence of Co considerably affected the local magnetic microstructure of the 119-Sn nuclei. This was probably due to the higher magnetic moment of Co, which induces transfer fields and polarization effects on the diamagnetic Sn atoms.

SUMO-specific peptidase 3 mediates the SUMO3 modification of BECN1 to repress cell autophagy in gliomas.

SUMO Specific Peptidase 3 (SENP3) is involved in the occurrence and development of various cancers. However, its effects on gliomas have been barely reported. Herein, this research was designed to probe the potential mechanisms of SENP3 mediating beclin-1(BECN1) SUMO3 modification in autophagy in gliomas. SENP3 expression in gliomas was analyzed through bioinformatic information. Clinical samples of glioma tissues were collected and frozen. SENP3 expression was evaluated with western blot. In glioma cells, autophagy- and apoptosis-related proteins, viability, and apoptosis were assessed with western blot and immunofluorescence, the cell counting kit-8, and flow cytometry, respectively. The SUMO modification of BECN1 and interactions between BECN1 and PIK3C3 were identified with Ni-NTA pull-down and co-immunoprecipitation assays, respectively. The tumor formation assay was carried out in nude mice for in vivo validation. Bioinformatics analysis predicted the overexpression of SENP3 in gliomas, which was confirmed in clinical samples and glioma cells. SENP3 silencing promoted autophagy and apoptosis and inhibited viability in glioma cells, which was counteracted by further autophagy inhibition. Mechanistically, SENP3 facilitated BECN1 deSUMOylation to mediate the SUMO3 modification of BECN1, thus impeding the formation of BECN1-PIK3C3 complexes. The loss of the SUMO part in BECN1 lowered the protein expression of LC3 and the value of LC3BII/LC3BI in glioma cells. Additionally, SENP3 silencing boosted autophagy and repressed tumor growth in mice, which was neutralized by further autophagy repression. SENP3 fosters the deSUMOylation of BECN1 to block the formation of BECN1-PIK3C3 complexes, thus restraining glioma cell autophagy.

Arabidopsis AGO1 N-terminal extension acts as an essential hub for PRMT5 interaction and post-translational modifications.

Plant ARGONAUTE (AGO) proteins play pivotal roles regulating gene expression through smallRNA(sRNA)-guided mechanisms. Among the 10AGO proteins in Arabidopsis thaliana, AGO1 stands out as the main effector of post-transcriptional gene silencing. Intriguingly, a specific region of AGO1, its N-terminal extension (NTE), has garnered attention in recent studies due to its involvement in diverse regulatory functions, including subcellular localization, sRNA loadingand interactions with regulatory factors. In the field of post-translational modifications (PTMs), little is known about arginine methylation in Arabidopsis AGOs. In this study, we show that NTE of AGO1 (NTEAGO1) undergoes symmetric arginine dimethylation at specific residues. Moreover, NTEAGO1 interacts with the methyltransferase PRMT5, which catalyzes its methylation. Notably, we observed that the lack of symmetric dimethylarginine has no discernible impact on AGO1's subcellular localization or miRNA loading capabilities. However, the absence of PRMT5 significantly alters the loading of a subgroup of sRNAs into AGO1 and reshapes the NTEAGO1 interactome. Importantly, our research shows that symmetric arginine dimethylation of NTEs is a common process among Arabidopsis AGOs, with AGO1, AGO2, AGO3and AGO5 undergoing thisPTM. Overall, this work deepens our understanding of PTMs in the intricate landscape of RNA-associated gene regulation.

Translational Utility of Organoid Models for Biomedical Research on Gastrointestinal Diseases.

Organoid models have recently been utilized to study 3D human-derived tissue systems to uncover tissuearchitecture and adultstem cellbiology. Patient-derived organoids unambiguously provide the most suitable in vitro system to study disease biology with the actual genetic background. With the advent of much improved and innovative approaches, patient-derived organoids can potentially be used in regenerative medicine. Various human tissues were explored to develop organoids due to their multifold advantage over the conventional in vitro cell line culture approach and in vivo models. Gastrointestinal (GI) tissues have been widely studied to establish organoids and organ-on-chip for screening drugs, nutraceuticals, and other small molecules having therapeutic potential. The function of channel proteins, transporters, and transmembrane proteins was also explained. The successful application of genome editing in organoids using the CRISPR-Cas approach has been reported recently. GI diseases such as Celiac disease (CeD), Inflammatory bowel disease (IBD), and common GI cancers have been investigated using several patient-derived organoid models. Recent advancements on organoid bio-banking and 3D bio-printing contributed significantly in personalized disease management and therapeutics. This article reviews the available literature on investigations and translational applications of patient-derived GI organoid models, notably on elucidating gut-microbial interaction and epigenetic modifications.

Time-dependent interaction modification generated from plant-soil feedback.

Pairwise interactions between species can be modified by other community members, leading to emergent dynamics contingent on community composition. Despite the prevalence of such higher-order interactions, little is known about how they are linked to the timing and order of species' arrival. We generate population dynamics from a mechanistic plant-soil feedback model, then apply a general theoretical framework to show that the modification of a pairwise interaction by a third plant depends on its germination phenology. These time-dependent interaction modifications emerge from concurrent changes in plant and microbe populations and are strengthened by higher overlap between plants' associated microbiomes. The interaction between this overlap and the specificity of microbiomes further determines plant coexistence. Our framework is widely applicable to mechanisms in other systems from which similar time-dependent interaction modifications can emerge, highlighting the need to integrate temporal shifts of species interactions to predict the emergent dynamics of natural communities.

A highly conserved tRNA modification contributes to C. albicans filamentation and virulence.

tRNA modifications play important roles in maintaining translation accuracy in all domains of life. Disruptions in the tRNA modification machinery, especially of the anticodon stem loop, can be lethal for many bacteria and lead to a broad range of phenotypes in baker's yeast. Very little is known about the function of tRNA modifications in host-pathogen interactions, where rapidly changing environments and stresses require fast adaptations. We found that two closely related fungal pathogens of humans, the highly pathogenic Candida albicans and its much less pathogenic sister species, Candida dubliniensis, differ in the function of a tRNA-modifying enzyme. This enzyme, Hma1, exhibits species-specific effects on the ability of the two fungi to grow in the hypha morphology, which is central to their virulence potential. We show that Hma1 has tRNA-threonylcarbamoyladenosine dehydratase activity, and its deletion alters ribosome occupancy, especially at 37°C-the body temperature of the human host. A C. albicans HMA1 deletion mutant also shows defects in adhesion to and invasion into human epithelial cells and shows reduced virulence in a fungal infection model. This links tRNA modifications to host-induced filamentation and virulence of one of the most important fungal pathogens of humans.IMPORTANCEFungal infections are on the rise worldwide, and their global burden on human life and health is frequently underestimated. Among them, the human commensal and opportunistic pathogen, Candida albicans, is one of the major causative agents of severe infections. Its virulence is closely linked to its ability to change morphologies from yeasts to hyphae. Here, this ability is linked-to our knowledge for the first time-to modifications of tRNA and translational efficiency. One tRNA-modifying enzyme, Hma1, plays a specific role in C. albicans and its ability to invade the host. This adds a so-far unknown layer of regulation to the fungal virulence program and offers new potential therapeutic targets to fight fungal infections.

Fatigue damage analysis method of offshore wind turbine foundation

The systems of offshore wind turbines are established in a complex marine environment, and are subjected to all kinds of ocean loadings such as waves, currents and wind for a long time. It is found that offshore wind turbine foundations are seldom damaged due to the problem of strength and stability under normal operation conditions. Most of the damages are caused by the fatigue damage under long-term loads. Aimed to this problem, the monopile foundation of offshore wind turbine is analyzed as an example in this study. The fatigue damage is analyzed systematically using the method of time-domain, combining the rain-flow counting method, S–N curve with linear and nonlinear fatigue damage models. In addition, a modified nonlinear fatigue damage model is proposed based on the Corten-Dolan and Manson-Halford nonlinear fatigue damage models, which can consider the modification of load interactions and the effect of loading sequence. In this way, the short-term fatigue damage value of offshore wind turbine foundation can be obtained. On the basis, the long-term probability distribution function of wind speed is obtained according to the actual monitoring results of wind load, and the fatigue damage value of the offshore wind turbine foundation in the design life can be obtained. Finally, a complete fatigue damage analysis method of offshore wind turbines is proposed, which is applicable to both short-term fatigue damage and long-term fatigue damage.

Effect of Alloying Elements on the Microstructure and Magnetic Properties of Mechanically Alloyed AlNiCo‐Based High‐Entropy Alloys

Herein, the effect of addition of Cu, Fe, and CuFe on microstructure and magnetic properties of equiatomic ternary AlNiCo alloy is reported. This addition of Cu, Fe, and CuFe to AlNiCo results in L12, B2, and mixed α + B2 phases, respectively, during the mechanical alloying (MA) and subsequent annealing process. The low‐temperature magnetic properties show that the addition of nonmagnetic Cu to AlNiCo enhances the coercivity, while Fe enhances the saturation magnetization value. Further from the study of magnetic properties, it is suggested that the phase segregation effects are minimum in MA process compared to melt process. It is also shown that the disorder plays a significant role in controlling the magnetic properties. The observed anomalous magnetic behavior is discussed in terms of modifications in exchange interactions between constituent elements due to chemical and structural disorder.

Cryo-EM structure of wheat ribosome reveals unique features of the plant ribosomes

Plants being sessile organisms exhibit unique features in ribosomes, which might aid in rapid gene expression and regulation in response to varying environmental conditions. Here, we present high-resolution structures of the 60S and 80S ribosomes from wheat, a monocot staple crop plant (Triticum aestivum). While plant ribosomes have unique plant-specific rRNA modification (Cm1847) in the peptide exit tunnel (PET), the zinc-finger motif in eL34 is absent, and uL4 is extended, making an exclusive interaction network. We note differences in the eL15-helix 11 (25S) interaction, eL6-ES7 assembly, and certain rRNA chemical modifications between monocot and dicot ribosomes. In eukaryotes, we observe highly conserved rRNA modification (Gm75) in 5.8S rRNA and a flipped base (G1506) in PET. These features are likely involved in sensing or stabilizing nascent chain. Finally, we discuss the importance of the universal conservation of three consecutive rRNA modifications in all ribosomes for their interaction with A-site aminoacyl-tRNA.

Heat-induced SUMOylation differentially affects bacterial effectors in plant cells.

Bacterial pathogens deliver effectors into host cells to suppress immunity. How host cells target these effectors is critical in pathogen-host interactions. SUMOylation, an important type of posttranslational modification in eukaryotic cells, plays a critical role in immunity, but its effect on bacterial effectors remains unclear in plant cells. In this study, using bioinformatic and biochemical approaches, we found that at least 16 effectors from the bacterial pathogen Pseudomonas syringae pv. tomato DC3000 are SUMOylated by the enzyme cascade from Arabidopsis thaliana. Mutation of SUMOylation sites on the effector HopB1 enhances its function in the induction of plant cell death via stability attenuation of a plant receptor kinase BRASSINOSTEROID INSENSITIVE 1 (BRI1)-ASSOCIATED RECEPTOR KINASE 1. By contrast, SUMOylation is essential for the function of another effector, HopG1, in the inhibition of mitochondria activity and jasmonic acid signaling. SUMOylation of both HopB1 and HopG1 is increased by heat treatment, and this modification modulates the functions of these 2 effectors in different ways in the regulation of plant survival rates, gene expression, and bacterial infection under high temperatures. Therefore, the current work on the SUMOylation of effectors in plant cells improves our understanding of the function of dynamic protein modifications in plant-pathogen interactions in response to environmental conditions.

Potential of Surface Functionalized Nanomaterials in Innovative Drug Development: A Mini-review

Abstract: The unique properties of nanomaterials (NMs) make them special entities for biomedical innovation and research. Early diagnosis and follow-up of diseases are easily possible with the help of nanotechnology and nanomedicine, which can help combat any medical condition. Surface functionalization with specific molecules might impart marked properties to NMs, leading to the modification of cellspecific interactions within the biological systems. This modification may provide excellent phenomena for innovative drug development. Modified NMs might play essential roles in various applications, i.e., in vivo diagnostics, magnetic resonance imaging (MRI), positron emission tomography (PET), etc. Functionalization of NMs with appropriate ligands, small molecules, or polymers assigned them enhanced stability, biocompatibility, and functionality for their novel and improved biological applications. Surface functionalized NMs might display enhanced antimicrobial, antidiabetic, and drug delivery potential for various applications. Different studies reported the potential of functionalized metallic nanoparticles in regenerative medicines. Conjugation of NMs with various molecules such as peptides, small ligands, polysaccharides, proteins, saturated and polyunsaturated fatty acids, siRNA, plasmids, and DNA, might be achieved by various reactions. Biomolecule-conjugated nanoparticles result in the production of hybrid NMs with specific and novel biological interactions in biological systems. Chemical treatment methods are considered among the most trusted and efficient functionalization methods. Some commonly used techniques and strategies of functionalization involve grafting to and grafting from methods, ligand exchange technique, covalent bonding, chemisorption, non-covalent interactions, electrostatic adsorption, etc. This brief review is dedicated to the surface functionalization of NMs with the latest development

Ion-Induced PIP2 Clustering with Martini3: Modification of Phosphate-Ion Interactions and Comparison with CHARMM36.

Phosphatidylinositol 4,5-bisphosphate (PIP2) is a critical lipid for cellular signaling. The specific phosphorylation of the inositol ring controls protein binding as well as clustering behavior. Two popular models to describe ion-mediated clustering of PIP2 are Martini3 (M3) and CHARMM36 (C36). Molecular dynamics simulations of PIP2-containing bilayers in solutions of potassium chloride, sodium chloride, and calcium chloride, and at two different resolutions are performed to understand the aggregation and the model parameters that drive it. The average M3 clusters of PIP2 in bilayers of 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine and PIP2 bilayers in the presence of K+, Na+, or Ca2+ contained 2.2, 2.6, and 6.4 times more PIP2 than C36 clusters, respectively. Indeed, the Ca2+-containing systems often formed a single large aggregate. Reparametrization of the M3 ion-phosphate Lennard-Jones interaction energies to reproduce experimental osmotic pressure of sodium dimethyl phosphate (DMP), K[DMP], and Ca[DMP]2 solutions, the same experimental target as C36, yielded comparably sized PIP2 clusters for the two models. Furthermore, C36 and the modified M3 predict similar saturation of the phosphate groups with increasing Ca2+, although the coarse-grained model does not capture the cooperativity between K+ and Ca2+. This characterization of the M3 behavior in the presence of monovalent and divalent ions lays a foundation to study cation/protein/PIP2 clustering.