Molecular Motion Research Articles

Photoinhibition of the hERG potassium channel PAS domain by ultraviolet light speeds channel closing

hERG potassium channels are critical for cardiac excitability. hERG channels have a Per-Arnt-Sim (PAS) domain at their N-terminus, and here, we examined the mechanism for PAS domain regulation of channel opening and closing (gating). We used TAG codon suppression to incorporate the noncanonical amino acid 4-benzoyl-L-phenylalanine (BZF), which is capable of forming covalent cross-links after photoactivation by ultraviolet (UV) light, at three locations (G47, F48, and E50) in the PAS domain. We found that hERG-G47BZF channels had faster closing (deactivation) when irradiated in the open state (at 0 mV) but showed no measurable changes when irradiated in the closed state (at −100 mV). hERG-F48BZF channels had slower activation, faster deactivation, and a marked rightward shift in the voltage dependence of activation when irradiated in the open (at 0 mV) or closed (at −100 mV) state. hERG-E50BZF channels had no measurable changes when irradiated in the open state (at 0 mV) but had slower activation, faster deactivation, and a rightward shift in the voltage dependence of activation when irradiated in the closed state (at −100mV), indicating that hERG-E50BZF had a state-dependent difference in UV photoactivation, which we interpret to mean that PAS underwent molecular motions between the open and closed states. Moreover, we propose that UV-dependent biophysical changes in hERG-G47BZF, F48BZF, and E50BZF were the direct result of photochemical cross-linking that reduced dynamic motions in the PAS domain and broadly stabilized the closed state relative to the open state of the channel.

Robust Algorithms for the Analysis of Fast-Field-Cycling Nuclear Magnetic Resonance Dispersion Curves

Fast-Field-Cycling (FFC) Nuclear Magnetic Resonance (NMR) relaxometry is a powerful, non-destructive magnetic resonance technique that enables, among other things, the investigation of slow molecular dynamics at low magnetic field intensities. FFC-NMR relaxometry measurements provide insight into molecular motion across various timescales within a single experiment. This study focuses on a model-free approach, representing the NMRD profile R1 as a linear combination of Lorentzian functions, thereby addressing the challenges of fitting data within an ill-conditioned linear least-squares framework. Tackling this problem, we present a comprehensive review and experimental validation of three regularization approaches to implement the model-free approach to analyzing NMRD profiles. These include (1) MF-UPen, utilizing locally adapted L2 regularization; (2) MF-L1, based on L1 penalties; and (3) a hybrid approach combining locally adapted L2 and global L1 penalties. Each method’s regularization parameters are determined automatically according to the Balancing and Uniform Penalty principles. Our contributions include the implementation and experimental validation of the MF-UPen and MF-MUPen algorithms, and the development of a “dispersion analysis” technique to assess the existence range of the estimated parameters. The objective of this work is to delineate the variance in fit quality and correlation time distribution yielded by each algorithm, thus broadening the set of software tools for the analysis of sample structures in FFC-NMR studies. The findings underline the efficacy and applicability of these algorithms in the analysis of NMRD profiles from samples representing different potential scenarios.

Anchoring Au nanoclusters into coordination polymers: A novel approach toward ATP detection and its application

Adenosine triphosphate (ATP) is the main source of energy required for all life activities and is used as a biomarker for diseases such as cancer. It is of great significance to design a novel fluorescent probe with favorable performance for monitoring the changes of ATP concentration. Herein, a fluorescence probe named ZnCPs@AuNCs for ATP sensing was designed and fabricated by integrating AuNCs into ZnCPs. The emission intensity of AuNCs was greatly enhanced upon the formation of the ZnCPs@AuNCs nanocomposites, which may be attributed to ZnCPs restricting the molecular motion of AuNCs. Upon the introduction of ATP, the fluorescence intensity at 564 nm of ZnCPs@AuNCs is quenched. According to this phenomenon, a sensitive and reliable ATP sensing platform was established. Moreover, ZnCPs@AuNCs were incorporated into a poly (vinyl alcohol) matrix for the fabrication of fluorescent film, which exhibited solid-state fluorescence. Inspired by the remarkable fluorescent properties of ZnCPs@AuNCs, the fluorescent hydrogel was prepared by mixing ZnCPs@AuNCs with κ-carrageenan, which demonstrated a response to ATP and favorable self-healing ability. This work presents a perspective of ZnCPs@AuNCs in multiple applications such as biosensing, fluorescent film, and hydrogel construction.

When surface-enhanced Raman spectroscopy meets complex biofluids: A new representation strategy for reliable and comprehensive characterization

BackgroundSurface-enhanced Raman spectroscopy (SERS) has gained increasing importance in molecular detection due to its high specificity and sensitivity. Complex biofluids (e.g., cell lysates and serums) typically contain large numbers of different bio-molecules with various concentrations, making it extremely challenging to be reliably and comprehensively characterized via conventional single SERS spectra due to uncontrollable electromagnetic hot spots and irregular molecular motions. The traditional approach of directly reading out the single SERS spectra or calculating the average of multiple spectra is less likely to take advantage of the full information of complex biofluid systems. ResultsHerein, we propose to construct a spectral set with unordered multiple SERS spectra as a novel representation strategy to characterize full molecular information of complex biofluids. This new SERS representation not only contains details from each single spectra but captures the temporal/spatial distribution characteristics. To address the ordering-independent property of traditional chemometric methods (e.g., the Euclidean distance and the Pearson correlation coefficient), we introduce Wasserstein distance (WD) to quantitatively and comprehensively assess the quality of spectral sets on biofluids. WD performs its superiority for the quantitative assessment of the spectral sets. Additionally, WD benefits from its independence of the ordering of spectra in a spectral set, which is undesirable for traditional chemometric methods. With experiments on cell lysates and human serums, we successfully achieve the verification for the reproducibility between parallel samples, the uniformity at different positions in the same sample, the repeatability from multiple tests at one location of the same sample, and the cardinality effect of the spectral set. SERS spectral sets also manage to distinguish different classes of human serums and achieve higher accuracy than the traditional prostate-specific antigen in prostate cancer classification. SignificanceThe proposed SERS spectral set is a robust representation approach in accessing full information of biological samples compared to relying on a single or averaged spectra in terms of reproducibility, uniformity, repeatability, and cardinality effect. The application of WD further demonstrates the effectiveness and robustness of spectral sets in characterizing complex biofluid samples, which extends and consolidates the role of SERS.

Impact of Sacrificial Hydrogen Bonds on the Structure and Properties of Rubber Materials: Insights from All-Atom Molecular Dynamics Simulations.

The inclusion of sacrificial hydrogen bonds is crucial for advancing high-performance rubber materials. However, the molecular mechanisms governing the impact of these bonds on material properties remain unclear, hindering progress in advanced rubber material research. This study employed all-atom molecular dynamics simulations to thoroughly investigate how hydrogen bonds affect the structure, dynamics, mechanics, and linear viscoelasticity of rubber materials. As the modified repeating unit ratio (β) increased, both interchain and intrachain hydrogen bond content rose, with interchain bonds playing a predominant role. This physical cross-linking network formed through interchain hydrogen bonds restricts molecular chain movement and relaxation and raises the glass transition temperature of rubber. Within a certain content of hydrogen bonds, the mechanical strength increases with increasing β. However, further increasing β leads to a subsequent decrease in the mechanical performance. Optimal mechanical properties were observed at β = 6%. On the other hand, a higher β value yields an elevated stress relaxation modulus and an extended stress relaxation plateau, signifying a more complex hydrogen-bond cross-linking network. Additionally, higher β increases the storage modulus, loss modulus, and complex viscosity while reducing the loss factor. In summary, this study successfully established the relationship between the structure and properties of natural rubber containing hydrogen bonds, providing a scientific foundation for the design of high-performance rubber materials.

Curing characteristics and performance of a bio-based polyurethane engineered sealant with high bonding strength: Effect of R value and chain extender content

Polyurethane (PU) engineering sealants can be used to fill construction joints and pavement cracks with excellent practical results. However, traditional engineering sealants have the disadvantages of poor strength and raw materials that are not environmentally friendly. In this paper, a novel composition system of bio-based polyurethane engineering sealant was developed. The effects of the isocyanate/macroglycol molar ratio (nNCO/nOH, R value) for component A and the contents of amine chain extender (AME) on the curing characteristics and properties of the PU sealant were investigated using a series of experiments. Firstly, the curing process of the sealant was studied by Fourier transform infrared spectroscopy (FTIR) test, surface drying time test and gel time experiments. Secondly, the basic physical properties of the sealant were studied by tensile and hardness tests. And the water resistance of the sealant was judged. Then, the characteristics of molecular movement of polyurethane sealant were analyzed by dynamic mechanical analysis (DMA). The tensile cross-sections of the specimens were observed by scanning electron microscopy (SEM). Finally, the thermal stability of sealants was studied by thermogravimetric (TG) analysis. The results indicated that the material developed in this research can be used as a high-performance engineering sealant in actual projects. The increase in the R value and the decrease in AME content resulted in a longer curing process of the sealant. The rise of R value and AME content was able to raise the tensile strength, bonding strength and hardness of the sealant. The water resistance of the sealant was better. Also, the glass transition temperature (Tg) and storage modulus could also be increased and the thermal stability of the previous stage could be reduced by increasing the R value and AME content. Considering both the performance and construction requirements, the optimum R value and AME contents are recommended to be 2.1 and 1.4%, respectively.

Novel Wide-Working-Temperature NaNO3-KNO3-Na2SO4 Molten Salt for Solar Thermal Energy Storage.

A novel ternary eutectic salt, NaNO3-KNO3-Na2SO4 (TMS), was designed and prepared for thermal energy storage (TES) to address the issues of the narrow temperature range and low specific heat of solar salt molten salt. The thermo-physical properties of TMS-2, such as melting point, decomposition temperature, fusion enthalpy, density, viscosity, specific heat capacity and volumetric thermal energy storage capacity (ETES), were determined. Furthermore, a comparison of the thermo-physical properties between commercial solar salt and TMS-2 was carried out. TMS-2 had a melting point 6.5 °C lower and a decomposition temperature 38.93 °C higher than those of solar salt. The use temperature range of TMS molten salt was 45.43 °C larger than that of solar salt, which had been widened about 13.17%. Within the testing temperature range, the average specific heat capacity of TMS-2 (1.69 J·K-1·g-1) was 9.03% higher than that of solar salt (1.55 J·K-1·g-1). TMS-2 also showed higher density, slightly higher viscosity and higher ETES. XRD, FTIR and Raman spectra SEM showed that the composition and structure of the synthesized new molten salt were different, which explained the specific heat capacity increasing. Molecular dynamic (MD) simulation was performed to explore the different macroscopic properties of solar salt and TMS at the molecular level. The MD simulation results suggested that cation-cation and cation-anion interactions became weaker as the temperature increased and the randomness of molecular motion increased, which revealed that the interaction between the cation cluster and anion cluster became loose. The stronger interaction between Na-SO4 cation-anion clusters indicated that TMS-2 molten salt had a higher specific heat capacity than solar salt. The result of the thermal stability analysis indicated that the weight losses of solar salt and TMS-2 at 550 °C were only 27% and 53%, respectively. Both the simulation and experimental study indicated that TMS-2 is a promising candidate fluid for solar power generation systems.

High temperature electrical breakdown and energy storage performance improved by hindering molecular motion in polyetherimide nanocomposites

Polyetherimide (PEI) is widely used as a material for high temperature and high power energy storage capacitors in new energy vehicles and other fields. However, as the temperature increases, the electrical conductivity increases and the breakdown strength decreases, which greatly reduces the energy storage density of the capacitor and limits the application range. In order to clarify the influence mechanism of high temperature on the breakdown and energy storage performance of dielectrics, this paper established a charge capture and molecular displacement (CTMD) breakdown model based on the expansion motion of molecular segments to study the charge transport and molecular chain motion process of PEI nanocomposites (PNCs) at high temperature. The results show that at 100 °C, compared with pure PEI, the internal maximum molecular displacement of PEI PNCs with appropriate doping content (3 wt%) is reduced by 28.79 %, and the breakdown strength is increased by 11.20 %. Appropriate nano-doping can effectively increase the movement difficulty of molecular chains and reduce the activation volume that provides energy for charge transport. Thus, charge transport is inhibited, current density is reduced, and Joule heat accumulation is avoided. Finally, the high temperature breakdown and energy storage performance are improved.

Microscopic insights on liquid–vapor phase change phenomena of R1336mzz(Z) nanofilm through molecular dynamics simulations

The ever-growing advances in electronics pose a critical cooling challenge. Two-phase heat transfer technology, with effective heat removal and no extra energy consumption, is emerging as a potential solution for sustainable thermal management. However, questions regarding phase change mechanisms are seemingly not addressed yet due to the limitation in time and space scales. In this work, a series of molecular dynamics simulations are performed where the R1336mzz(Z) liquid film rests over a smooth copper substrate. The molecular system starts with a nanofilm thickness of 4–10 nm and then is subjected to non-equilibrium heating (350, 400, 450, and 500 K) to initiate liquid-to-vapor phase change. Depending on the impacts of film thickness and wall temperature, four distinctive phase change scenarios are identified, i.e., diffusive evaporation, pseudo-diffusive evaporation, explosive boiling, and stable explosive boiling. The characteristics of these phase change modes are explicated from the perspectives of molecular motion, vaporization rate, temperature evolution, heat flux, and interfacial resistance. The phase change mode has a strong dependence on two aspects: improving heat transfer to breakup potential barrier and slowing energy dissipation to support formation of bubble embryos. The insight may deliver better understandings of phase change mechanism and applications of liquid refrigerants.

Photo‐Responsive Hydrogen‐Bonded Molecular Networks Capable of Retaining Crystalline Periodicity after Isomerization

AbstractThe molecular conformation, crystalline morphology, and properties of photochromic organic crystals can be controlled through photoirradiation, making them promising candidates for functional organic materials. However, photochromic porous molecular crystals with a networked framework structure are rare due to the difficulty in maintaining space that allows for photo‐induced molecular motion in the crystalline state. This study describes a photo‐responsive single crystal based on hydrogen‐bonded (H‐bonded) network of dihydrodimethylbenzo[e]pyrene derivative 4BDHP. A crystal composed of H‐bonded undulate layers, 4BDHP‐2, underwent photo‐isomerization in the crystalline state due to loose stacking of the layers. Particularly, enantio‐pure crystal (S,S)‐4BDHP‐2 allowed to reveal the structure of the photoisomerized crystal, in which the closed form (4BDHP) and open form (4CPD) were arranged alternately with keeping crystalline periodicity, although side reactions were also implied. The present proof‐of‐concept system of a photochromic framework that retains crystalline periodicity after photo‐isomerization may provide new light‐driven porous functional materials.

Dynamics and Internal Structure Evolution during the Glass Transition of the Ethylene-Cyclic Olefin Copolymers: A Molecular Dynamics Simulation.

Amorphous ethylene-cyclic olefin copolymers (COCs) which can be used in cell phone lenses and prefilled syringes have attracted increasing attention due to their excellent and tunable thermal properties. In order to better explain the influence of COC microstructure (cyclic olefin types and content) on the glass transition mechanism, we used molecular dynamics (MD) simulations to track the evolution of free volume, diffusion coefficients, atomic mobility, trans conformation probabilities, and characteristic parameters of α-relaxation kinetics during the quenching process. MD results show that for the classic COC E-co-NB (ethylene-norbornene copolymer), an increase in cyclic olefin content from 25 to 50 mol % reduces atomic mobility, limiting the molecular chain movement at higher temperatures and improving Tg. Compared to NB, the more rigid rings in tricyclopentadiene (TCPD) and exo-1,4,4a,9,9a,10-hexahydro-9,10(1',2')-bridged phenylidene-1,4-bridged methylideneanthracene (HBM) have the following effects: (1) reducing the thermal expansion coefficient and overall chain mobility; (2) enhancing the diffusion energy barrier; (3) promoting the formation of local ordered structures; (4) accelerating α-relaxation dynamics at high temperatures and improving the dynamic fragility m. These lead to an upward shift in the temperature region where chain movement is limited and thus improve Tg and high-temperature dimensional stability. In this simulation, the correlation equation between Tg, m, and the microstructural parameters of COCs is established, which is of great significance for the development of COCs with high performance.

Photoresponsive Biomimetic Functions by Light-Driven Molecular Motors in Three Dimensionally Printed Liquid Crystal Elastomers.

Despite the fascinating developments in design and synthesis of artificial molecular machines operating at the nanoscales, translating molecular motion along multiple length scales and inducing mechanical motion of a three-dimensional macroscopic entity remains an important challenge. The key to addressing this amplification of motion relies on the effective organization of molecular machines in a well-defined environment. By taking advantage of long-range orientational order and hierarchical structures of liquid crystals and unidirectional rotation of light-driven molecular motors, we report here photoresponsive biomimetic functions of liquid crystal elastomers (LCEs) by the repetitive unidirectional rotation of molecular motors using 3D printing. Molecular motors were built in the main chain of liquid crystals oligomers to serve as photoactuators. The oligomers were then used as the ink, and liquid crystal elastomers with different morphologies were printed. The obtained LCEs are able to conduct multiple types of motions including bending, helical coiling, closing of petals, and flipping of wings of a butterfly upon UV illumination, which paves the way for future design of responsive materials with enhanced complex actuating functions.

Photo-Responsive Hydrogen-Bonded Molecular Networks Capable of Retaining Crystalline Periodicity after Isomerization.

The molecular conformation, crystalline morphology, and properties of photochromic organic crystals can be controlled through photoirradiation, making them promising candidates for functional organic materials. However, photochromic porous molecular crystals with a networked framework structure are rare due to the difficulty in maintaining space that allows for photo-induced molecular motion in the crystalline state. This study describes a photo-responsive single crystal based on hydrogen-bonded (H-bonded) network of dihydrodimethylbenzo[e]pyrene derivative 4BDHP. A crystal composed of H-bonded undulate layers, 4BDHP-2, underwent photo-isomerization in the crystalline state due to loose stacking of the layers. Particularly, enantio-pure crystal (S,S)-4BDHP-2 allowed to reveal the structure of the photoisomerized crystal, in which the closed form (4BDHP) and open form (4CPD) were arranged alternately with keeping crystalline periodicity, although side reactions were also implied. The present proof-of-concept system of a photochromic framework that retains crystalline periodicity after photo-isomerization may provide new light-driven porous functional materials.

Thermoplastic polyimide with good comprehensive performance based on carbazole groups and short flexible linkages

AbstractThermoplastic polyimides (TPIs) can meet the requirements of advanced electronic packaging such as flexible copper clad laminate (FCCL) applied under extreme conditions, attributed to their excellent thermal stability, mechanical properties, electrical insulation and chemical resistance. With the increasing demands for electronic devices, such as applications in high‐frequency communication, it is highly desirable to develop high‐performance TPI with good thermoplasticity, thermal stability, mechanical properties and dielectric properties. However, there is a trade‐off between thermoplasticity and other properties. Herein, we introduce an effective strategy to afford TPIs with good performance by copolymerization of a diamine monomer consisted of a coplanar aromatic carbazole group and a short flexible linkage methylene group. On the one hand, short flexible linkages help improve the flexibility of polymer chains and are not too much to enable small‐scale molecular motions below Tg. On the other hand, coplanar aromatic donor groups benefit to strong charge transfer complex (CTC) interaction and π‐π stacking interaction. Based on this strategy, the resultant TPI possesses good thermoplasticity with a proper Tg of 348 °C. Meanwhile, it preserves a low coefficient thermal expansion of 48 ppm K−1, low dielectric constant/dielectric loss factor of 3.27/0.0073 at 10 GHz, and tensile strength of ca. 78 MPa.

Dynamic embedding of effective harmonic normal mode vibrations in all-atomistic energy gap fluctuations: Case study of light harvesting 2 complex.

Environmental effects in excitation energy transfer have mostly been modeled by baths of harmonic oscillators, but to what extent such modeling provides a reliable description of actual interactions between molecular systems and environments remains an open issue. We address this issue by investigating fluctuations in the excitation energies of the light harvesting 2 complex using a realistic all-atomistic simulation of the potential energy surface. Our analyses reveal that molecular motions exhibit significant anharmonic features, even for underdamped intramolecular vibrations. In particular, we find that the anharmonicity contributes to the broadening of spectral densities and substantial overlaps between neighboring peaks, which complicates the meaning of mode frequencies constituting a bath model. Thus, we develop a strategy to construct a minimally underdamped harmonic bath that has a clear connection to all-atomistic dynamics by utilizing actual normal modes of molecules but optimizing their frequencies such that the resulting bath model can best reproduce the all-atomistic simulation results. By subtracting the underdamped contribution from the entire fluctuations, we also show that identifying a residual spectral density representing all other contributions with overdamped behavior is possible. We find that this can be fitted well with a well-established analytic form of a spectral density function or, alternatively, modeled as explicit time dependent fluctuations with muti-exponential or power law type correlation functions. We provide an assessment and the implications of these possibilities. The approach presented here can also serve as a general strategy to construct a simplified bath model that can effectively represent the underlying all-atomistic bath dynamics.

Modification of the Dielectric and Thermal Properties of Organic Frameworks Based on Nonterminal Epoxy Liquid Crystal with Silicon Dioxide and Titanium Dioxide.

A nonterminal liquid crystal epoxy monomer is used to create an epoxy-amine network with a typical diamine 4,4'diaminodiphenylmethane. The plain matrix is compared to matrices modified with inorganic fillers: TiO2 or SiO2. Conditions of the curing reaction and glass transition temperatures in the cured products are determined through differential scanning calorimetry and broadband dielectric spectroscopy. The curing process is also followed through optical and electrical observations. The dielectric response of all investigated networks reveals a segmental α-process related to structural reorientation (connected to the glass transition). In all products, a similar process associated with molecular motions of polar groups also appears. The matrix modified with TiO2 exhibits two secondary relaxation processes (β and γ). Similar processes were observed in the pure monomer. An advantage of the network with the TiO2 filler is a shorter time or lower temperature required for optimal curing conditions. The physical properties of cured matrices depend on the presence of a nematic phase in the monomer and nonterminal functional groups in the aliphatic chains. In effect, such cured matrices can have more flexibility and internal order than classical resins. Additional modifiers used in this work shift the glass transition above room temperature and influence the fragility index in both cases.

Label-free detection and profiling of individual solution-phase molecules.

Most chemistry and biology occurs in solution, in which conformational dynamics and complexation underlie behaviour and function. Single-molecule techniques1 are uniquely suited to resolving molecular diversity and new label-free approaches are reshaping the power of single-molecule measurements. A label-free single-molecule method2-16 capable of revealing details of molecular conformation in solution17,18 would allow a new microscopic perspective of unprecedented detail. Here we use the enhanced light-molecule interactions in high-finesse fibre-based Fabry-Pérot microcavities19-21 to detect individual biomolecules as small as 1.2 kDa, a ten-amino-acid peptide, with signal-to-noise ratios (SNRs) >100, even as the molecules are unlabelled and freely diffusing in solution. Our method delivers 2D intensity and temporal profiles, enabling the distinction of subpopulations in mixed samples. Notably, we observe a linear relationship between passage time and molecular radius, unlocking the potential to gather crucial information about diffusion and solution-phase conformation. Furthermore, mixtures of biomolecule isomers of the same molecular weight and composition but different conformation can also be resolved. Detection is based on the creation of a new molecular velocity filter window and a dynamic thermal priming mechanism that make use of the interplay between optical and thermal dynamics22,23 and Pound-Drever-Hall (PDH) cavity locking24 to reveal molecular motion even while suppressing environmental noise. New in vitro ways of revealing molecular conformation, diversity and dynamics can find broad potential for applications in the life and chemical sciences.

Molecular dynamics study of confined liquid film viscosity in Constant-Pressure and Constant-Distance systems

Viscosity changes in confined liquids have been explored using experimental techniques including surface force apparatus (SFA) and fiber wobbling method (FWM), revealing different magnitudes of viscosity increment as the gap between confining solid surfaces decreases. To address this disparity, we performed molecular dynamics simulations to gain insights into the mechanisms of viscosity changes in confined liquid UV-curable resin films used in nanoimprint lithography. Solid surfaces were fixed to maintain a constant pressure or distance, resembling SFA and FWM, respectively. Consistent with experimental results, our simulations confirmed that the viscosity increases with decreasing solid–solid gaps, notably, more pronounced in the constant-distance system than in the constant-pressure one. However, the two systems exhibited no distinct difference in the liquid molecular distribution. By introducing a new concept of free volume change rate, we conducted an in-depth analysis of liquid molecular motion, revealing more active motion in the constant-pressure system, particularly in the central region between the solid surfaces. This motion correlated positively with atomic vibrations of the confining surfaces. Our findings emphasize that different confinement conditions (constant pressure or constant distance) distinctly alter the liquid molecular motion and thus the magnitude of viscosity, underscoring the necessity for precise characterization of the rheological properties of confined UV-curable resins.

Enhanced Aggregation-Induced Delayed Electrochemiluminescence Triggered by Spatial Perturbation of Organic Dots.

Development of highly efficient, heavy-metal-free electrochemiluminescence (ECL) materials is attractive but still challenging. Herein, we report an aggregation-induced delayed ECL (AIDECL) active organic dot (OD) composed of a tert-butoxy-group-substituted benzophenone-dimethylacridine compound, which shows high ECL efficiency. The resultant ODs exhibit 2.1-fold higher ECL efficiency compared to control AIDECL-active ODs. Molecular stacking combined with theoretical calculations suggests that tert-butoxy groups effectively participate in the intermolecular interactions, further inhibiting the molecular motions in the aggregated states and thus accelerating radiative decay. On the basis of these ODs exhibiting excellent ECL performance, a proof-of-concept biosensor is constructed for the detection of miR-16 associated with Alzheimer's disease, which demonstrates excellent detection ability with the limit of detection of 1.7 fM. This work provides a new approach to improve the ECL efficiency and enriches the fundamental understanding of the structure-property relationship.

Molecular Docking Improved with Human Spatial Perception Using Virtual Reality.

Adaptive steered molecular dynamics (ASMD) is a computational biophysics method in which an external force is applied to a selected set of atoms or a specific reaction coordinate to induce a particular molecular motion. Virtual reality (VR) based methods for protein-ligand docking are beneficial for visualizing on-the-fly interactive molecular dynamics and performing promising docking trajectories. In this paper, we propose a novel method to guide ASMD with optimal trajectories collected from human experiences using interactive molecular dynamics in virtual reality (iMD-VR). We also explain the benefits of using VR as a tool for expediting the process of ligand binding, outlining an experimental protocol that enables iMD-VR users to guide Amprenavir into and out of the binding pockets of HIV-1 protease and recreate their respective crystallographic binding poses within 5 minutes. Later, we discuss our analysis of the results from iMD-VR-assisted ASMD simulation and assess its performance compared to a standard ASMD simulation. From the accuracy point of view, our proposed method calculates higher Potential Mean Force (PMF) values consistently relative to a standard ASMD simulation with an almost twofold increase in all the experiments. Finally, we describe the novelty of the research and discuss results showcasing a faster and more effective convergence of the ligand to the protein's binding site as compared to a standard molecular dynamics simulation, proving the effectiveness of VR in the field of drug discovery. Future work includes the development of an artificial intelligence algorithm capable of predicting optimal binding trajectories for many protein-ligand pairs, as well as the required force needed to steer the ligand to follow the said trajectory.