The phase separation of oppositely-charged polyelectrolytes in solution is of current interest . In this work we study the driving force for polyelectrolyte complexation using molecular dynamics simulations. We calculate the potential of mean force between poly(lysine) and poly(glutamate) oligomers using three different forcefields, an atomistic force field and two coarse-grained force fields. There is excellent qualitative agreement between all forcefields which suggests that the molecular nature of water does not play a significant role. We find that the driving force for association is entropic in all cases when small ions either neutralize the poly-ions, or are in excess. The removal of all counterions switches the driving force, making complexation energetic. This is an important finding, that suggests that the entropy of complexation is dominated by the counterions, although we see no evidence of counterion condensation.The simulations shed insight into the mechanism of complex coacervation and question several of the approximations currently used in theoretical studies of the phenomena.

The noble elements constitute the simplest group of atoms. At low temperatures or high pressures, they freeze into the face-centered cubic (fcc) crystal structure (except helium). This paper investigates neon, argon, krypton, and xenon by molecular dynamics using the simplified atomic potentials recently proposed by Deiters and Sadus [J. Chem. Phys. 150, 134504 (2019)], which are parameterized using data from accurate ab initio quantum-mechanical calculations by the coupled-cluster approach at the single-double-triple level. We compute the fcc freezing lines and find good agreement with the empirical values. At low pressures, predictions are improved by including many-body corrections.Hidden scale invariance of the potential-energy function is established by showing that mean-squared displacement and the static structure factor are invariant along the lines of constant excess entropy (isomorphs). The isomorph theory of melting [Pedersen et al., Nat. Commun. 7, 12386 (2016)] is used to predict from simulations at a single state point the freezing line's shape, the entropy of melting, and the Lindemann parameter of the crystal at melting. Finally, our results suggest that the body-centered cubic crystal is the thermodynamically stable phase at high pressures.

Liquid–liquid phase separation (LLPS) between tyrosine- and arginine-rich peptides are of biological importance. To understand the interactions between proteins in the condensed phase in close analogy to complex coacervation, we run multiple umbrella calculations between oligomers containing tyrosine (pY) and arginine (pR). We find pR-pY complexation to be energetically driven. Metadynamics simulations on monomers suggest that this energy of complexation is correlated with the number of π-cation bonds. Free energy calculations for the binding between pairs of poly glutamate-pR dimers show striking similarities between this process and LLPS. These calculations suggest that proteins containing arginine and tyrosine residues do not undergo complexation followed by coacervation. The mechanism, rather, is akin to phase separation of neutral polyion pairs.

Alzheimer disease is a neurodegenerative disease that is signified by cognitive decline, memory loss, and erratic behavior. Dendrimers are a type of polymer that has a well-defined structure, a high degree of molecular uniformity, and a low polydispersity which have shown to be effective intracellular drug carriers for bring down the in numerous cases. The data reported by the clinical trials and chemical bonds of dendrimers loading and biological properties that may be used in the bringing out the treatment of nano formulation for Alzheimer disease. Below-range dendrimers have an unlocked figure, but higher-range dendrimers have a more globular and dense structure so handling is difficult. Dendrimers are similar in size to a variety of biological structures; for example, fifth-generation polyamidoamine (PAMAM) dendrimers are similar in size and shape to haemoglobin (5.5 nm diameter). Each generation of dendrimer is described in terms of size, shape, molecular weight, and the number of surface functional groups, with increasing growth specified in terms of 'generation number.' In contrast, Hawker and Frechet were the first to report the convergent approach. A stepwise repeating reaction strategy is used to synthesize dendrimers radically from a central core. The value of dendrimers as drug carriers is discussed in this paper. The information presented in this article can provide useful references for further studies on making dendrimers and applications.

Microglia is cells of mesodermal/mesenchymal origin that migrate into the central nervous system (CNS) to form resident macrophages inside the special brain microenvironment. Intact with both neuronal and non-neuronal cells, microglia is highly active cells. Continuous process extension and retraction allows microglia to scan the brain parenchyma for threats. They are also able to change their morphology from ramified to amoeboid, which is a sign of cell activity. In response to pleiotropic stimuli such as neurotransmitters, cytokines, and plasma proteins, microglia express a diverse range of receptors. As controllers of synaptic activities and phagocytosis of developing neurons, they serve a critical role in the healthy brain and have significant effects on synaptic plasticity and adult neurogenesis. A frequent cause of hypoparathyroidism is a mutation in the gene glial cells missing-2 (GCM2). Neonatal hypoparathyroidism has an amorphic recessive GCM2 mutation, while autosomal dominant hypoparathyroidism has a dominant-negative GCM2 mutation. Curiously, familial isolated hyperparathyroidism has been associated with activating GCM2 mutation. In addition to seizures, neurocognitive impairment, carpopedal spasm, tingling and numbness are common clinical manifestations of hypoparathyroidism. Biogenic amines are a group of four neurotransmitters that belong to that category and these include serotonin, dopamine, norepinephrine, and epinephrine. Numerous antidepressants prevent the reuptake from occurring the brain-gut axis is hardwired through the CNS, enteric nervous system (ENS), neuroendocrine linkages and highly innervated nerve plexuses.

We use molecular dynamics simulations to study the thermodynamics and kinetics of alanine dipeptide isomerization at the air−water interface. Thermodynamically, we find an affinity of the dipeptide to the interface. This affinity arises from stabilizing intramolecular interactions that become unshielded as the dipeptide is desolvated. Kinetically, we consider the rate of transitions between the α L and β conformations of alanine dipeptide and evaluate it as a continuous function of the distance from the interface using a recent extension of transition path sampling, TPS+U. The rate of isomerization at the Gibbs dividing surface is suppressed relative to the bulk by a factor of 3. Examination of the ensemble of transition states elucidates the role of solvent degrees of freedom in mediating favorable intramolecular interactions along the reaction pathway of isomerization. Near the air−water interface, water is less effective at mediating these intramolecular interactions.

The pathophysiological processes of dementia and cognitive impairment are linked to advanced glycation end products (AGEs) and their receptor (RAGE).The neurofibrillary tangles (NFTs) of abnormally hyperphosphorylated tau protein and senile plaques (SPs), which are brought on by amyloid beta (Aβ) deposition, are the hallmarks of Alzheimer’s disease (AD), a progressive neurodegenerative condition. Advanced glycation end products that are produced as a result of vascular dysfunction are bound by the receptor for advanced glycation end products (RAGE). Dementia and cognitive impairment could develop when RAGE binds to Aβ and produces reactive oxygen species, aggravating Aβ buildup and ultimately resulting in SPs and NFTs. RAGE could be a more powerful biomarker than Aβ because it is implicated in early AD. The resident immune cells in the brain known as microglia are essential for healthy brain function. Microglia is prominent in the amyloid plaques’ outside border as well as their central region in Alzheimer’s disease. Microglial cells, in the opinion of some authors, actively contribute to the formation of amyloid plaques. In this review, we first discuss the early diagnosis of dementia and cognitive impairment, and then detail the interaction between RAGE and Aβ and Tau that is necessary to cause dementia and cognitive impairment pathology, and it is anticipated that the creation of RAGE probes will help in the diagnosis and treatment of dementia and cognitive impairment.

We present a time-dependent variational method to learn the mechanisms of equilibrium reactive processes and efficiently evaluate their rates within a transition path ensemble. This approach builds off of the variational path sampling methodology by approximating the time-dependent commitment probability within a neural network ansatz. The reaction mechanisms inferred through this approach are elucidated by a novel decomposition of the rate in terms of the components of a stochastic path action conditioned on a transition. This decomposition affords an ability to resolve the typical contribution of each reactive mode and their couplings to the rare event. The associated rate evaluation is variational and systematically improvable through the development of a cumulant expansion. We demonstrate this method in both over- and under-damped stochastic equations of motion, in low-dimensional model systems, and in the isomerization of a solvated alanine dipeptide. In all examples, we find that we can obtain quantitatively accurate estimates of the rates of the reactive events with minimal trajectory statistics and gain unique insights into transitions through the analysis of their commitment probability.