ABSTRACT
Developing phase diagrams for inhomogeneous systems in thermodynamics is difficult, in part, due to the large phase space and the possibility of unstable and metastable solutions arising from first-order phase transitions. Pseudo-arclength continuation (PAC) is a method that allows one to trace out stable and unstable solutions of nonlinear systems. Typically, PAC utilizes the Jacobian in order to implement Newton (or quasi-Newton) steps. In this work, we present a Jacobian-free PAC method that is amenable to the usual workflows in inhomogeneous thermodynamics. We demonstrate our method in systems that have first-order phase transitions, including a novel example of polyelectrolyte complex coacervation in confinement, where multiple surface phase transitions occur and can overlap with one another.
ABSTRACT
The creation of synthetic materials that emulate the complexity of natural systems, such as enzymes, remains a challenge in biomimicry. Here, we present a simple yet effective strategy to introduce substrate selectivity and dynamic responsiveness into an enzyme-mimetic supramolecular material. We achieved this by anchoring γ-cyclodextrin to a fluorene-modified Lys/Cu2+ assembly, which mimics copper-dependent oxidase. The binding affinity among the components was examined using 1H NMR, isothermal titration calorimetry (ITC), and theoretical simulation. The γ-cyclodextrin acts as a host, forming a complex with the fluorenyl moiety and aromatic substrates of specific sizes. This ensures the proximity of the substrate reactive groups to the copper center, leading to size-selective enhancement of aromatic substrate oxidation, particularly favoring biphenyl substrates. Notably, α- and ß-cyclodextrins do not exhibit this effect, and the native oxidase lacks this selectivity. Additionally, the binding affinity of the aromatic substrate to the catalyst can be dynamically tuned by adding α-cyclodextrin or by irradiating with different wavelengths in the presence of competitive azo-guests, resulting in switched oxidative activities. This approach offers a new avenue for designing biomimetic materials with tailorable active site structures and catalytic properties.
ABSTRACT
Dynamic self-assembly has significant implications in the regulation of the enzyme activities. In this study, we present a histidine-based enzyme-mimicking catalyst, formed by the self-assembly of carefully-engineered FH-based short peptides with hemin, showcasing switchable catalytic activity of hemin due to externally induced reversible inclusion of a cucurbit[7]uril-peptide hybrid. 1H NMR, ITC and theoretical simulation are employed to examine the binding affinity between the guest and host components, and UV-vis spectra are used to investigate changes in the hemin coordination environment. The histidine segment of the short peptide can be partially shielded by the cucurbituril and released following addition of the azo compound, leading to a decrease and subsequent restoration of the histidine-hemin coordination affinity and hemin activity. The photoisomeriziable nature of the azo compound enabled the activation of FHH/hemin activity to be switched on and off by exposure to different wavelengths of light. During the operation, the Phe residue remained within the cucurbituril, allowing reversible inclusion and exposure of the histidine residues. The hemin stayed connected to FHH/cucurbit[7]uril hybrid, preventing the severe aggregation of hemin and irreversible deactivation. This work may provide insights into engineering the dynamic behaviors of the cofactor-dependent catalytic assemblies.
ABSTRACT
Metallo-polyelectrolytes are versatile materials for applications like filtration, biomedical devices, and sensors, due to their metal-organic synergy. Their dynamic and reversible electrostatic interactions offer high ionic conductivity, self-healing, and tunable mechanical properties. However, the knowledge gap between molecular-level dynamic bonds and continuum-level material properties persists, largely due to limited fabrication methods and a lack of theoretical design frameworks. To address this critical gap, we present a framework, combining theoretical and experimental insights, highlighting the interplay of molecular parameters in governing material properties. Using stereolithography-based additive manufacturing, we produce durable metallo-polyelectrolytes gels with tunable mechanical properties based on metal ion valency and polymer charge sparsity. Our approach unveils mechanistic insights into how these interactions propagate to macroscale properties, where higher valency ions yield stiffer, tougher materials, and lower charge sparsity alters material phase behavior. This work enhances understanding of metallo-polyelectrolytes behavior, providing a foundation for designing advanced functional materials.
ABSTRACT
Dynamic DNA-based nanodevices offer versatile molecular-level operations, but the majority of them suffer from sluggish kinetics, impeding the advancement of device complexity. In this work, we present the self-assembly of a cationic peptide with DNA to expedite toehold-mediated DNA strand displacement (TMSD) reactions, a fundamental mechanism enabling the dynamic control and actuation of DNA nanostructures. The target DNA is modified with a fluorophore and a quencher, so that the TMSD process can be monitored by recording the time-dependent fluorescence changes. The boosting effect of the peptides is found to be dependent on the peptide/DNA N/P ratio, the toehold/invader binding affinity, and the ionic strength with stronger effects observed at lower ionic strengths, suggesting that electrostatic interactions play a key role. Furthermore, we demonstrate that the cationic peptide enhances the responsiveness and robustness of DNA machinery tweezers or logic circuits (AND and OR) involving multiple strand displacement reactions in parallel and cascade, highlighting its broad utility across DNA-based systems of varying complexity. This work offers a versatile approach to enhance the efficiency of toehold-mediated DNA nanodevices, facilitating flexible design and broader applications.
Subject(s)
Cations , DNA , Nanostructures , Peptides , DNA/chemistry , Peptides/chemistry , Nanostructures/chemistry , Cations/chemistry , Nanotechnology/methods , Osmolar Concentration , Static Electricity , Fluorescent Dyes/chemistryABSTRACT
In recent years, molecular dynamics (MD) simulations have emerged as an essential tool for understanding the structure, dynamics, and phase behavior of charged soft matter systems. To explore phenomena across greater length and time scales in MD simulations, molecules are often coarse-grained for better computational performance. However, commonly used force fields represent particles as hard-core interaction centers with point charges, which often overemphasizes the packing effect and short-range electrostatics, especially in systems with bulky deformable organic molecules and systems with strong coarse-graining. This underscores the need for an efficient soft-core model to physically capture the effective interactions between coarse-grained particles. To this end, we implement a soft-core model uniting the Gaussian core model with smeared electrostatic interactions that is phenomenologically equivalent to recent theoretical models. We first parametrize it generically using water as the model solvent. Then, we benchmark its performance in the OpenMM toolkit for different boundary conditions to highlight a computational speedup of up to 34 × compared to commonly used force fields and existing implementations. Finally, we demonstrate its utility by investigating how boundary polarizability affects the adsorption behavior of a polyelectrolyte solution on perfectly conducting and nonmetal boundaries.
ABSTRACT
Polyelectrolytes, such as poly(acrylic acid) (PAA), can effectively mitigate CaCO3 scale formation. Despite their success as antiscalants, the underlying mechanism of binding of Ca2+ to polyelectrolyte chains remains unresolved. Through all-atom molecular dynamics simulations, we constructed an adsorption isotherm of Ca2+ binding to sodium polyacrylate (NaPAA) and investigated the associated binding mechanism. We find that the number of calcium ions adsorbed [Ca2+]ads to the polymer saturates at moderately high concentrations of free calcium ions [Ca2+]aq in the solution. This saturation value is intricately connected with the binding modes accessible to Ca2+ ions when they bind to the polyelectrolyte chain. We identify two dominant binding modes: the first involves binding to at most two carboxylate oxygens on a polyacrylate chain, and the second, termed the high binding mode, involves binding to four or more carboxylate oxygens. As the concentration of free calcium ions [Ca2+]aq increases from low to moderate levels, the polyelectrolyte chain undergoes a conformational transition from an extended coil to a hairpin-like structure, enhancing the accessibility to the high binding mode. At moderate concentrations of [Ca2+]aq, the high binding mode accounts for at least one-third of all binding events. The chain's conformational change and its consequent access to the high binding mode are found to increase the overall Ca2+ ion binding capacity of the polyelectrolyte chain.
ABSTRACT
Enzymatic catalysis presents an eco-friendly, energy-efficient method for lignin degradation. However, challenges arise due to the inherent incompatibility between enzymes and native lignin. In this work, we introduce a supramolecular catalyst composed of fluorenyl-modified amino acids and Cu2+, designed based on the aromatic stacking of the fluorenyl group, which can operate in ionic liquid environments suitable for the dissolution of native lignin. Amino acids and halide anions of ionic liquids shape the copper site's coordination sphere, showcasing remarkable catechol oxidase-mimetic activity. The catalyst exhibits thermophilic property, and maintains oxidative activity up to 75 °C, which allows the catalyzed degradation of the as-dissolved native lignin with high efficiency even without assistance of the electron mediator. In contrast, at this condition, the native copper-dependent oxidase completely lost its activity. This catalyst with superior stability and activity offer promise for sustainable lignin valorization through biocatalytic routes compatible with ionic liquid pretreatment, addressing limitations in native enzymes for industrially relevant conditions.
Subject(s)
Ionic Liquids , Ionic Liquids/chemistry , Lignin/chemistry , Copper , Oxidoreductases , Catalysis , Amino AcidsABSTRACT
We construct a coarse-grained molecular dynamics model based on poly(ethylene oxide) and lithium bis(trifluoromethane)sulfonimide salt to examine the combined effects of temperature and salt concentration on the transport properties. Salt doping notably slows the dynamics of polymer chains and reduces ion diffusivity, resulting in a glass transition temperature increase proportional to the salt concentration. The polymer diffusion is shown to be well represented by a modified Vogel-Fulcher-Tamman (M-VFT) equation that accounts for both the temperature and salt concentration dependence. Furthermore, we find that, at any temperature, the concentration dependence of the conductivity is well described by the product of its infinite dilution value and a correction factor accounting for the reduced segmental mobility with increasing salt concentration. These results highlight the important role of polymer segmental mobility in the salt concentration dependence of ion conductivity for temperatures near and above the glass transition.
ABSTRACT
Mixing solutions of oppositely charged macromolecules can result in liquid-liquid phase separation into a polymer-rich coacervate phase and a polymer-poor supernatant phase. Here, we show that charge asymmetry in the constituent polymers can slow down the coarsening dynamics, with an apparent growth exponent that deviates from the well-known 1/3 for neutral systems and decreases with increasing degrees of charge asymmetry. Decreasing solvent quality accelerates the coarsening dynamics for asymmetric mixtures but slows down the coarsening dynamics for symmetric mixtures. We rationalize these results by examining the interaction potential between merging droplets.
ABSTRACT
Toehold-mediated DNA strand displacement (TMSD) is a powerful tool for controlling DNA-based molecular reactions and devices. However, the slow kinetics of TMSD reactions often limit their efficiency and practical applications. Inspired by the chemical structures of natural DNA-operating enzymes (e.g., helicase), we designed lysine-rich peptides to self-assemble with DNA-based systems. Our approach allows for accelerating the TMSD reactions, even during multiple displacement events, enhancing their overall efficiency and utility. We found that the acceleration is dependent on the peptide's sequence, length, and concentration as well as the length of the DNA toehold domain. Molecular dynamics simulations revealed that the peptides promote toehold binding between the double-stranded target and the single-stranded invader, thereby facilitating strand displacement. Furthermore, we integrated our approach into a horseradish peroxidase-mimicking DNAzyme, enabling the dynamic modulation of enzymatic functions on and off. We anticipate that the established acceleration of strand displacement reactions and the modulation of enzymatic activities offer enhanced functionality and control in the design of programmable DNA-based nanodevices.
Subject(s)
DNA, Catalytic , DNA, Catalytic/metabolism , DNA/chemistry , KineticsABSTRACT
Challenges persist in replicating enzyme-like active sites with functional group arrangements in supramolecular catalysis. In this study, we present a supramolecular material comprising Fmoc-modified histidine and copper. We also investigated the impact of noncanonical amino acids (δmH and εmH), isomers of histidine, on the catalytic process. The Fmoc-δmH-based nanoassembly exhibits an approximately 15-fold increase in oxidative activity and an â¼50-fold increase in hydrolytic activity compared to Fmoc-εmH (kcat/Km). This distinction arises from differences in basicity and ligation properties between the ε- and δ-nitrogen of histidine. The addition of guanosine monophosphate further enhances the oxidative activity of the histidine- and methylated histidine-based catalysts. The Fmoc-δmH/Cu2+-based nanoassembly catalyzes the oxidation/hydrolysis cascade of 2',7'-dichlorofluorescein diacetate, benefiting from the synergistic effect between the copper center and the nonligating ε-nitrogen of histidine. These findings advance the biomimetic catalyst design and provide insights into the mechanistic role of essential residues in natural systems.
Subject(s)
Biomimetics , Histidine , Catalysis , Copper , Histidine/chemistry , Hydrolysis , Nitrogen , Oxidative StressABSTRACT
DNA is self-assembled with Fmoc-amino acids and Cu2+ to construct a supramolecular catechol oxidase-mimetic catalyst, which exhibits remarkable activity in catalyzing colorimetric reactions. This catalytic system is used for the detection of DNA hybridization with a high selectivity and a low detection limit.
Subject(s)
Colorimetry , Oxidoreductases , DNA/chemistry , Catechol Oxidase , Amino Acids , Limit of DetectionABSTRACT
We have engineered a colorimetric sensor capable of selective and sensitive detection of amino acids. This sensor employs a supramolecular copper-dependent oxidase mimic as the probe, stemming from our prior research. The oxidase mimic is constructed through the self-assembly of commercially available guanosine monophosphate (GMP), Fmoc-lysine, and Cu2+. It catalyzes the formation of a red product with a maximum absorbance at 510 nm. The changes in color and absorbance are responsive to both the concentrations and types of amino acids present. This effect is most pronounced in the presence of histidine, with a detection limit (LOD) of 6.4 nM. Furthermore, the catalytic probe can distinguish histidine from histamine and imidazole propionate, as well as 1-methyl-histidine from 3-methyl-histidine, based on their distinct coordination capacities with copper. This underscores the high selectivity of the sensing platform. Both theoretical simulations and experimental results (including UV-vis spectra, fluorescence, and EPR) indicate that the amino acids may engage in copper center coordination, thereby impeding O2 access to copperâa pivotal aspect of the oxidase catalysis. This sensing platform, characteristic of its swift response, simple fabrication, and exceptional sensitivity and selectivity, can also be applied to detect other biological analytes such as nucleotides. It holds potential for use in environmental and biochemical analyses.
Subject(s)
Colorimetry , Copper , Colorimetry/methods , Copper/chemistry , Histidine/chemistry , Catalysis , OxidoreductasesABSTRACT
End-tethered polyelectrolytes are widely used to modify substrate properties, particularly for lubrication or wetting. External stimuli, such as pH, salt concentration, or an electric field, can induce profound structural responses in weak polyelectrolyte brushes, which can be utilized to further tune substrate properties. We study the structure and electroresponsiveness of weak polyacid brushes using an inhomogeneous theory that incorporates both electrostatic and chain connectivity correlations at the Debye-Hückel level. Our calculation shows that a weak polyacid brush swells under the application of a negative applied potential, in agreement with recent experimental observation. We rationalize this behavior using a scaling argument that accounts for the effect of the surface charge. We also show that the swelling behavior has a direct influence on the differential capacitance, which can be modulated by the solvent quality, pH, and salt concentration.
ABSTRACT
Large cell self-consistent field theory (SCFT) solutions for a neat, micelle-forming diblock copolymer melt, initialized using the structure of a Lennard-Jones fluid, reveal the existence of a vast number of liquid-like states, with free energies of order 10-3 kBT per chain higher than the body-centered cubic (bcc) state near the order-disorder transition (ODT). Computation of the structure factor for these liquids at temperatures below the ODT indicates that their intermicellar distance is slightly swollen compared to bcc. In addition to providing a mean-field picture of the disordered micellar state, the number of liquid-like states and their near-degeneracy with the equilibrium bcc morphology suggest that self-assembly of micelle-forming diblock copolymers navigates a rugged free energy landscape with many local minima. This picture provides a basis for the anomalously slow ordering kinetics of particle-forming diblock copolymer melts observed in experiments.
ABSTRACT
The de novo design of artificial biocatalysts with enzyme-like active sites and catalytic functions has long been an attractive yet challenging goal. In this study, we present a nucleotide-Cu2+ complex, synthesized through a one-pot approach, capable of catalyzing ortho-hydroxylation reactions resembling those of minimalist monooxygenases. Both experimental and theoretical findings demonstrate that the catalyst, in which Cu2+ coordinates with both the nucleobase and phosphate moieties, forms a ternary-complex intermediate with H2O2 and tyramine substrates through multiple weak interactions. The subsequent electron transfer and hydrogen (or proton) transfer steps lead to the ortho-hydroxylation of tyramine, where the single copper center exhibits a similar function to natural dicopper sites. Moreover, Cu2+ bound to nucleotides or oligonucleotides exhibits thermophilic catalytic properties within the temperature range of 25 °C to 75 °C, while native enzymes are fully deactivated above 35 °C. This study may provide insights for the future design of oxidase-mimetic catalysts and serve as a guide for the design of primitive metallocentre-dependent enzymes.
Subject(s)
Copper , Mixed Function Oxygenases , Mixed Function Oxygenases/chemistry , Mixed Function Oxygenases/metabolism , Copper/chemistry , Oxidation-Reduction , Nucleotides/metabolism , Hydrogen Peroxide , TyramineABSTRACT
Enzymes fold into unique three-dimensional structures to distribute their reactive amino acid residues, but environmental changes can disrupt their essential folding and lead to irreversible activity loss. The de novo synthesis of enzyme-like active sites is challenging due to the difficulty of replicating the spatial arrangement of functional groups. Here, we present a supramolecular mimetic enzyme formed by self-assembling nucleotides with fluorenylmethyloxycarbonyl (Fmoc)-modified amino acids and copper. This catalyst exhibits catalytic functions akin those of copper cluster-dependent oxidases, and catalytic performance surpasses to date-reported artificial complexes. Our experimental and theoretical results reveal the crucial role of periodic arrangement of amino acid components, enabled by fluorenyl stacking, in forming oxidase-mimetic copper clusters. Nucleotides provide coordination atoms that enhance copper activity by facilitating the formation of a copper-peroxide intermediate. The catalyst shows thermophilic behavior, remaining active up to 95 °C in an aqueous environment. These findings may aid the design of advanced biomimetic catalysts and offer insights into primordial redox enzymes.
Subject(s)
Copper , Metalloproteins , Copper/chemistry , Biomimetics , Oxidoreductases , Amino Acids , NucleotidesABSTRACT
Biomolecular assembly typically exhibits enthalpy-entropy compensation (EEC) behavior whose molecular origin remains a long-standing puzzle. While water restructuring is believed to play an important role in EEC, its contribution to the entropy and enthalpy changes, and how these changes relate to EEC, remains poorly understood. Here, we show that water reorganization entropy/enthalpy can be obtained by exploiting the temperature dependence in effective, implicit-solvent potentials. We find that the different temperature dependencies in the hydrophobic interaction, rooted in water reorganization, result in substantial variations in the entropy/enthalpy change, which are responsible for EEC. For lower-critical-solution-temperature association, water reorganization entropy dominates the free-energy change at the expense of enthalpy; for upper-critical-solution-temperature association, water reorganization enthalpy drives the process at the cost of entropy. Other effects, such as electrostatic interaction and conformation change of the macromolecules, contribute much less to the variations in entropy/enthalpy.