Solvation Structures and Transport Mechanisms of Cations in Water-in-Bisalt Electrolytes for High-Concentration Lithium-Ion Batteries Revealed by Molecular Dynamics Simulations.

The development of safe and cost-effective electrolytes for rechargeable batteries is currently underway. While water-based electrolytes hold promise, their restricted electrochemical stability window poses a challenge. Combining multiple ionic species emerges as a promising strategy to broaden this stability window and optimize Li-ion battery performance. This study focuses on dual-cation electrolytes, which blend lithium and potassium acetates to enhance the electrochemical characteristics of the solution at high concentrations. We investigated the solvation structure of each ion and its interactions on a molecular level. Our analysis reveals that ion clusters and aggregates are formed through shared acetate and water molecules at high salt concentrations. Furthermore, the residence time analyses of atom pairs indicate that cations diffuse in vehicular mode at low concentrations. In contrast, they switch to a structural mode at high concentrations due to diminishing water content. This study offers a comprehensive model for exploring diverse solvation structures of cations and gaining insights into their diffusion mechanisms within water-in-bisalt electrolytes for aqueous Li-ion batteries.

Water-Ion Interaction Determines the Mobility of Ions in Highly Concentrated Aqueous Electrolytes.

Solvation engineering plays a critical role in tailoring the performance of batteries, particularly through the use of highly concentrated electrolytes, which offer heterogeneous solvation structures of mobile ions with distinct electrochemical properties. In this study, we employed spectroscopic techniques and molecular dynamics simulations to investigate mixed-cation (Li+/K+) acetate aqueous electrolytes. Our research unravels the pivotal role of water in facilitating ion transport within a highly viscous medium. Notably, Li+ cations primarily form ion aggregates, predominantly interacting with acetate anions, while K+ cations emerge as the principal charge carriers, which is attributed to their strong interaction with water molecules. Intriguingly, even at a concentration as high as 40 m, a substantial amount of water molecules persistently engages in hydrogen bonding with one another, creating mobile regions rich in K+ ions. Our observations of a redshift of the OH stretching band of water suggest that the strength of the hydrogen bond alone cannot account for the expansion of the electrochemical stability window. These findings offer valuable insights into the cation transfer mechanism, shedding light on the contribution of water-bound cations to both the ion conductivity and the electrochemical stability window of aqueous electrolytes for rechargeable batteries. Our comprehensive molecular-level understanding of the interplay between cations and water provides a foundation for future advances in solvation engineering, leading to the development of high-performance batteries with improved energy storage and safety profiles.

The hot sites of α-synuclein in amyloid fibril formation.

The role of alpha-synuclein (αS) amyloid fibrillation has been recognized in various neurological diseases including Parkinson's Disease (PD). In early stages, fibrillation occurs by the structural transition from helix to extended states in monomeric αS followed by the formation of beta-sheets. This alpha-helix to beta-sheet transition (αßT) speeds up the formation of amyloid fibrils through the formation of unstable and temporary configurations of the αS. In this study, the most important regions that act as initiating nuclei and make unstable the initial configuration were identified based on sequence and structural information. In this regard, a Targeted Molecular Dynamics (TMD) simulation was employed using explicit solvent models under physiological conditions. Identified regions are those that are in the early steps of structural opening. The trajectory was clustered the structures characterized the intermediate states. The findings of this study would help us to better understanding of the mechanism of amyloid fibril formation.

Multifunctional Acidocin 4356 Combats Pseudomonas aeruginosa through Membrane Perturbation and Virulence Attenuation: Experimental Results Confirm Molecular Dynamics Simulation.

A longstanding awareness in generating resistance to common antimicrobial therapies by Gram-negative bacteria has made them a major threat to global health. The application of antimicrobial peptides as a therapeutic agent would be a great opportunity to combat bacterial diseases. Here, we introduce a new antimicrobial peptide (∼8.3 kDa) from probiotic strain Lactobacillus acidophilus ATCC 4356, designated acidocin 4356 (ACD). This multifunctional peptide exerts its anti-infective ability against Pseudomonas aeruginosa through an inhibitory action on virulence factors, bacterial killing, and biofilm degradation. Reliable performance over tough physiological conditions and low hemolytic activity confirmed a new hope for the therapeutic setting. Antibacterial kinetic studies using flow cytometry technique showed that the ACD activity is related to the change in permeability of the membrane. The results obtained from molecular dynamic (MD) simulation were perfectly suited to the experimental data of ACD behavior. The structure-function relationship of this natural compound, along with the results of transmission electron microscopy analysis and MD simulation, confirmed the ability of the ACD aimed at enhancing bacterial membrane perturbation. The peptide was effective in the treatment of P. aeruginosa infection in mouse model. The results support the therapeutic potential of ACD for the treatment of Pseudomonas infections.IMPORTANCE Multidrug-resistant bacteria are a major threat to global health, and the Pseudomonas bacterium with the ability to form biofilms is considered one of the main causative agents of nosocomial infections. Traditional antibiotics have failed because of increased resistance. Thus, finding new biocompatible antibacterial drugs is essential. Antimicrobial peptides are produced by various organisms as a natural defense mechanism against pathogens, inspiring the possible design of the next generation of antibiotics. In this study, a new antimicrobial peptide was isolated from Lactobacillus acidophilus ATCC 4356, counteracting both biofilm and planktonic cells of Pseudomonas aeruginosa A detailed investigation was then conducted concerning the functional mechanism of this peptide by using fluorescence techniques, electron microscopy, and in silico methods. The antibacterial and antibiofilm properties of this peptide may be important in the treatment of Pseudomonas infections.

Effects of Linker Flexibility and Conformational Changes of IP3 Receptor on Split Luciferase Complementation Assay.

BACKGROUND: IP3-induced Ca2+ release, mediated by IP3R, is one of the most momentous cellular signaling mechanisms that regulate in a wide variety of essential cellular functions. Involvement of disrupted IP3 signaling pathways in numerous pathophysiology conditions is implicated to find the best methods for its measurement. Hence, several different biosensors have developed to monitor temporal changes of IP3 by using the IP3-binding domain of IP3 receptors. OBJECTIVES: Based on a previous study, we developed and characterized a series of bioluminescent biosensors using the human type-II IP3 receptor ligand binding domain (residues 1-604), named LAIRE (luminescent analyzer for IP3 receptor element) to study the effect of flexible and rigid linkers on the luminescence intensity of split luciferase. The effect of a mutation in IP3 binding residues and suppressor domain in the IP3 binding domain on luciferase complementary assay is also investigated. MATERIALS AND METHODS: In the present study, first IP3-binding domain (residues 1-604) of IP3-receptor type 2 (LAIRE) was fused between complementary non-functional fragments of firefly luciferase and then the rigid linker sequence (LLRAIEAQQHLL), selected by ProDA database, introduced between Nluc and ligand binding domain and compared with that of the flexible linker ((GGGGS)2) in LAIRE chimera. The IP3-insensitive mutant of the biosensor was constructed using the Stratagene QuikChange® procedure. In order to the analysis of the dynamical movements of selected structures in the large-scale, coarse-graining method of molecular dynamics simulation (1µs) was applied. RESULTS: As expected, the flexible linker brings two inactive fragments of luciferase together relative to the rigid linker and leads to complementation of luciferase activity, which is detected using luciferin. However, this conformational flexibility in linker increases background to noise ratio and attenuates fold induction. CONCLUSIONS: It seems that the ligand binding properties of IP3 binding core make it more suitable for the design of biosensor than the ligand binding domain.

Trypanothione Reductase Gene Mutations in Meglumine Antimoniate Resistant Isolates from Cutaneous Leishmaniasis Patients Using Molecular Dynamics Method.

BACKGROUND: In this study, mutations in the tripanothion reductase of Leishmania tropica isolated from Iran was investigated using sequencing and simulation of the enzyme by the molecular dynamic method. METHODS: Fifteen susceptible and 15 clinical resistant L. tropica specimens were collected from skin lesions from different regions of Iran in 2017. After DNA extraction, trypanothione reductase (TRYR or TPR), gene fragment was amplified using PCR and sequencing methods. In the case of structural mutations, the components were simulated by molecular dynamics using the GROMACS software. RESULTS: Some structural mutations were observed in 9 amino acids surrounding the active site of the TRYR gene of L. tropica with three-dimensional trypanothione reductase alteration. CONCLUSION: Change in the active site of TRYR of L. tropica, could probably contribute to the development of resistant L. tropica to glucantime. Because of the likely occurrence of mutations in glucantime as well as the ease of development of L. tropica resistant populations, more samples are needed to demonstrate the relationship between mutations in this enzyme and clinical resistance to glucantime. On the other hand, it is recommended that enzymatic studies be performed to confirm the role of mutation in the function and expression of trypanothione reductase in glucantime resistant and susceptible populations.

OligoCOOL: A mobile application for nucleotide sequence analysis.

Today smartphones are inseparable parts of modern life and are capable of performing many desktop computers' tasks such as scientific analysis with greater convenience. Here, we present OligoCOOL, which is an Android application for analyzing nucleic sequences. This application enables users to perform several common biomedical analyses for a given nucleotide sequence. OligoCOOL is a freely accessible Android app at http://bioinf.modares.ac.ir/software/OligoCOOL, which can be a suitable tool for the experimental design in the laboratories. This application also can be used to learn the basics of nucleotide sequence analysis. © 2019 International Union of Biochemistry and Molecular Biology, 47(2): 201-206, 2019.

A comparative study of structure, stability and function of sc-tenecteplase in the presence of stabilizing osmolytes.

The aim of the present study was to investigate the effect of three routine drug excipients, as osmolytes, in three different concentrations, on structure, thermal stability and the activity of single-chain (sc-) tenecteplase. To see the influence of trehalose, mannitol, and sucrose on the structure, stability and function of sc-tenecteplase, thermal stability, fluorescence, circular dichroism (CD) and enzyme kinetic measurements and molecular docking studies were carried out. To measure the effect of osmolytes on stability of sc-tenecteplase, thermodynamic parameters (transition temperature (Tm), standard enthalpy change (ΔH°), standard entropy change (ΔS°) and ΔG°, the standard Gibbs free energy change, were determined from heat-induced transition curves of the protein in absence and presence of each osmolyte. It was observed that all three osmolytes acted as an enhancer for the sc-tenecteplase stability, with varying efficacies and efficiencies. The results of the kinetic study showed that the activity of sc-tenecteplase is increased in the presence of osmolytes. The near-UV and far-UV CD studies showed transfer of Trp, Phe and Tyr residues to a more flexible environment in the presence of osmolytes. The sc-tenecteplase fluorescence quenching suggested the more polar location of Trp residues. Molecular docking studies revealed that (i) Gibbs free energy of interaction between the osmolyte and sc-tenecteplase is negative, and (ii) hydrogen bond and hydrophobic interactions dominate within the interaction sites.

Insights into the molecular interaction between two polyoxygenated cinnamoylcoumarin derivatives and human serum albumin.

Ligand binding studies on human serum albumin (HSA) are crucial in determining the pharmacological properties of drug candidates. Here, two representatives of coumarin-chalcone hybrids were selected and their binding mechanism was identified via thermodynamics techniques, curve resolution analysis and computational methods at molecular levels. The binding parameters were derived using spectroscopic approaches and the results point to only one pocket located near the Trp214 residue in subdomain IIA of HSA. The protein tertiary structure was altered during ligand binding and formed an intermediate structure to create stronger ligand binding interactions. The best binding mode of the ligand was initially estimated by docking on an ensemble of HSA crystallographic structures and by molecular dynamics (MD) simulations. Per residue interaction energies were calculated over the MD trajectories as well. Reasonable agreement was found between experimental and theoretical results about the nature of binding, which was dominated by hydrogen bonding and van der Waals contributions.