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Water dynamics in nanochannels are altered by confinement, particularly in small carbon nanotubes (CNTs). However, the mechanisms behind these effects remain unclear. To address these issues, we carried out extensive molecular dynamics (MD) simulations to investigate the structure and dynamics of water inside CNTs of different sizes (length of 20 nm and diameters vary from 0.8 nm to 5.0 nm) at different temperatures (from 200 K to 420 K). The radial density profile of water inside CNTs shows a single peak near the CNT walls for small nanotubes. For CNTs with larger sizes, water molecules are arranged into coaxial tubular sheets, the number of which increases with the CNT size. Subdiffusive behavior is observed for ultranarrow CNTs with diameters of 0.8 nm and 1 nm. As the size of CNTs increases, Fickian diffusion becomes evident. The hydrogen bond correlation function of water inside CNT decays slower than in bulk water, and the decay rate decreases as we increase the diameter of the CNTs. In large CNTs, the hydrogen bond lifetime of the innermost layer is shorter than the other layers and depends on temperature. Additional analysis of our results reveals that water molecules along the CNT axis show a non-Arrhenius to Arrhenius diffusion crossover. In general, the diffusion transition temperature is higher than that of bulk water, but it depends on the size of the CNT. 

DNA polymerase β (pol β ) is a member of the X- family of DNA polymerases that catalyze the distributive addition of nucleoside triphosphates during base excision DNA repair. Previous studies showed that the enzyme was phosphorylated in vitro with PKC at two serines (44 and 55), causing loss of DNA polymerase activity but not DNA binding. In this work, we have investigated the phosphorylation-induced conformational changes in DNA polymerase β in the presence of Mg ions. We report a comprehensive atomic resolution study of wild type and phosphorylated DNA polymerase using molecular dynamics (MD) simulations. The results are examined via novel methods of internal dynamics and energetics analysis to reveal the underlying mechanism of conformational transitions observed in DNA pol β . The results show drastic conformational changes in the structure of DNA polymerase β due to S44 phosphorylation. Phosphorylation-induced conformational changes transform the enzyme from a closed to an open structure. The dynamic cross-correlation shows that phosphorylation enhances the correlated motions between the different domains. Centrality network analysis reveals that the S44 phosphorylation causes structural rearrangements and modulates the information pathway between the Lyase domain and base pair binding domain. Further analysis of our simulations reveals that a critical hydrogen bond (between S44 and E335) disruption and the formation of three additional salt bridges are potential drivers of these conformational changes. In addition, we found that two of these additional salt bridges form in the presence of Mg ions on the active sites of the enzyme. These results agree with our previous study of DNA pol β S44 phosphorylation without Mg ions which predicted the deactivation of DNA pol β . However, the phase space of structural transitions induced by S44 phosphorylation is much richer in the presence of Mg ions. 

Water transport inside carbon nano-tubes (CNTs) has attracted considerable attention due to its nano-fluidic properties, its importance in nonporous systems, and the wide range of applications in membrane desalination and biological medicine. Recent studies show an enhancement of water diffusion inside nano-channels depending on the size of the nano-confinement. However, the underlying mechanism of this enhancement is not well understood yet. In this study, we performed Molecular Dynamics (MD) simulations to study water flow inside CNT systems. The length of CNTs considered in this study is 20 nm, but their diameters vary from 1 to 10 nm. The simulations are conducted at temperatures ranging from 260 K to 320 K. We observe that water molecules are arranged into coaxial water tubular sheets. The number of these tubular sheets depends on the CNT size. Further analysis reveals that the diffusion of water molecules along the CNT axis deviates from the Arrhenius temperature dependence. The non-Arrhenius relationship results from a fragile liquid-like water component persisting at low temperatures with fragility higher than that of the bulk water. 

The cytotoxic self-aggregation of β-amyloid (Aβ) peptide and islet amyloid polypeptide (IAPP) is implicated in the pathogenesis of Alzheimer’s disease (AD) and Type 2 diabetes (T2D), respectively. Increasing evidence, particularly the co-deposition of Aβ and IAPP in both brain and pancreatic tissues, suggests that Aβ and IAPP cross-interaction may be responsible for a pathological link between AD and T2D. Here, we examined the nature of IAPP-Aβ40 co-aggregation and its inhibition by small molecules. In specific, we characterized the kinetic profiles, morphologies, secondary structures and toxicities of IAPP-Aβ40 hetero-assemblies and compared them to those formed by their homo-assemblies. We demonstrated that monomeric IAPP and Aβ40 form stable hetero-dimers and hetero-assemblies that further aggregate into β-sheet-rich hetero-aggregates that are toxic (cell viability <50%) to both PC-12 cells, a neuronal cell model, and RIN-m5F cells, a pancreatic cell model for β-cells. We then selected polyphenolic candidates to inhibit IAPP or Aβ40 self-aggregation and examined the inhibitory effect of the most potent candidate on IAPP-Aβ40 co-aggregation. We demonstrated that epigallocatechin gallate (EGCG) form inter-molecular hydrogen bonds with each of IAPP and Aβ40. We also showed that EGCG reduced hetero-aggregate formation and resulted in lower β-sheets content and higher unordered structures in IAPP-Aβ40-EGCG samples. Importantly, we showed that EGCG is highly effective in reducing the toxicity of IAPP-Aβ40 hetero-aggregates on both cell models, specifically at concentrations that are equivalent to or are 2.5-fold higher than the mixed peptide concentrations. To the best of our knowledge, this is the first study to report the inhibition of IAPP-Aβ40 co-aggregation by small molecules. We conclude that EGCG is a promising candidate to prevent co-aggregation and cytotoxicity of IAPP-Aβ40, which in turn, contribute to the pathological link between AD and T2D.