Topological Conformations Research Articles

GTAM: a molecular pretraining model with geometric triangle awareness.

Molecular representation learning is pivotal for advancing deep learning applications in quantum chemistry and drug discovery. Existing methods for molecular representation learning often fall short of fully capturing the intricate interactions within chemical bonds of 2D topological graphs and the multifaceted effects of 3D geometric conformations. To overcome these challenges, we present a novel contrastive learning strategy for molecular representation learning, named Geometric Triangle Awareness Model (GTAM). This method integrates innovative molecular encoders for both 2D graphs and 3D conformations, enabling the accurate capture of geometric dependencies among edges in graph-based molecular structures. Furthermore, GTAM is bolstered by the development of two contrastive training objectives designed to facilitate the direct transfer of edge information between 2D topological graphs and 3D geometric conformations, enhancing the functionality of the molecular encoders. Through extensive evaluations on a range of 2D and 3D downstream tasks, our model has demonstrated superior performance over existing approaches. The test code and data of GTAM are available online at https://github.com/StellaHxy/GTAM.

Stimulus-Responsive Four-Stranded DNA Nanoring Assembly to Host Multiple Nanosilver Clusters for Cooperatively Enhanced Fluorescence Biosensing.

Exploring the ability of four-stranded DNA nanorings (fsDNRs) to host multiple nanosilver clusters (NAgCs) for cooperatively amplifiable fluorescence biosensing to a specific initiator (tI*) is fascinating. By designing three DNA single strands and three analogous stem-loop hairpins, we developed a functional fsDNR through sequential cross-opening and overlapped hybridization. Note that a substrate strand (SS) was programmed with six modules: two severed splits (sT and sT') of NAgCs template, two sequestered segments by a middle unpaired spacer, and a partition for tI*-recognizable displacement, while sT and sT' were also tethered in two ends of three hairpins. At first, a triple dsDNA complex with stimulus-responsiveness was formed to guide the specific binding to tI*, while the exposed toehold of the SS activated the forward cascade hybridization of three hairpins, until the ring closure in the tailored self-assembly pathway for forming the fsDNR. The resulting four duplexes forced each pair of sT/sT' to be merged as the parent template in four nicks, guiding the preferential synthesis of four clusters in the shared fsDNR, thereby cooperatively amplifying the green fluorescence signal for sensitive assay of tI*. Meanwhile, the topological conformation of fsDNR can be stabilized by the as-formed cluster adducts to rivet the pair of two splits in the nicks. Benefitting from the self-enhanced effect of multiple emitters, this label-free fluorescent sensing strategy features simplicity, rapidity, and high on-off contrast, without involving complicated nucleic acid amplifiers.

Polar topological bubbles in (K,Na)NbO3-based single crystals via synergetic phase and defect engineering

The investigations of polar topological conformations have become one of the hotspots due to their multitudinous physical properties and potential applications in emerging electronic devices. However, constructing polar topologies in bulk form is exceedingly challenging. In this study, bubble domains with different polar topologies, including flux-closure and half-closure, are successfully achieved in Cu-doped (K,Na)(Nb,Ta)O3 single crystals by elaborately adjusting the phase structure and defect dipoles. The coexistence of orthorhombic and tetragonal phases results in a flattened free energy landscape, while the presence of a high concentration of defect dipoles in local regions leads to the generation of the strong internal electric field, further modifying the energy profile. The interplay of various types of energies gives rise to the smooth rotation of the polar vectors, facilitating the formation of topological structures. These findings provide a practical method for constructing topological bubble domains in bulk materials, thereby enriching the understanding of the physical properties arising from topological structures.

Single-molecule analysis of solvent-responsive mechanically interlocked ring polymers and the effects of nanoconfinement from coarse-grained simulations.

In this study, we simulate mechanically interlocked semiflexible ring polymers inspired by the minicircles of kinetoplast DNA (kDNA) networks. Using coarse-grained molecular dynamics simulations, we investigate the impact of molecular topological linkage and nanoconfinement on the conformational properties of two- and three-ring polymer systems in varying solvent qualities. Under good-quality solvents, for two-ring systems, a higher number of crossing points lead to a more internally constrained structure, reducing their mean radius of gyration. In contrast, three-ring systems, which all had the same crossing number, exhibited more similar sizes. In unfavorable solvents, structures collapse, forming compact configurations with increased contacts. The morphological diversity of structures primarily arises from topological linkage rather than the number of rings. In three-ring systems with different topological conformations, structural uniformity varies based on link types. Extreme confinement induces isotropic and extended conformations for catenated polymers, aligning with experimental results for kDNA networks and influencing the crossing number and overall shape. Finally, the flat-to-collapse transition in extreme confinement occurs earlier (at relatively better solvent conditions) compared to non-confined systems. This study offers valuable insights into the conformational behavior of mechanically interlocked ring polymers, highlighting challenges in extrapolating single-molecule analyses to larger networks such as kDNA.

Gel transition of active triblock copolymers

The self-propulsion of active matter leads to many non-equilibrium self-organization phenomena, and the conformational freedom of polymer chains can produce unique equilibrium self-assembly behaviors, which stimulates cross-disciplinary research between active matter and polymer physics. In this work, we use molecular dynamics simulations to investigate the modulation of self-propulsion activity on the gel transition of ABA triblock copolymers. The research results indicate that under different active forces and attractive strengths, the gel states formed by ABA copolymers can be divided into three types: stable polymer gels with stable percolation paths and uniform spatial distribution, dynamic polymer gels with constantly changing percolation path and strand conformation, and collapsed polymer gels aggregating into large percolating clusters. The spatial uniformity of active gels is related not only to the concentration fluctuation during the formation of the network, but also to the inconsistent movement of the network chains caused by the activity, which is manifested in the rotation of crosslinking points in the flexible system and the directional movement of the bundles along their contour directions in the semi-flexible and rigid systems. In terms of topological conformation of polymer networks, when the attractive strength between A blocks is strong, the proportion of loop increases with the active force increasing. When attractive strength is weak, inter- and intra-chain binding are unstable, and the conformation is easily changed by the activity drive, noise and other chain collisions, so the proportion of loop decreases with the active force increasing. The branching number of crosslinking points varies with active force, which is not only affected by the attraction strength, but also related to the rigidity of the network chain. Generally, the branch number of crosslinking points in semi-flexible networks is larger than that in flexible and rigid networks. In addition, the directional motion of active polymers induces anomalous diffusion in stable polymer gels. This study contributes to the understanding of the collective behavior of active polymers and serves as a guide for designing and implementing active polymeric materials.

Non-spherical assemblies of chitin nanocrystals by drop impact assembly

Preparing complex non-spherical assemblies of elongated nanoparticles and exploring their topological conformations is a challenge due to liquid crystals' mobility and elastic distortion. Here, we fabricated a variety of non-spherical liquid crystal assemblies of chitin nanocrystals (ChNCs) in a coagulation bath containing sodium triphosphate (STP) by drop impact assembly method, and the forming mechanism and internal topology were systematically investigated. The collection height, ChNCs concentration, and STP concentration have significant influence on the shape and size of the assembled structures. Long-range ordered structures and long-lived topological textures of the ChNCs liquid crystal can be obtained since a molecular interaction of hydrogen bonding and electrostatic attractions between ChNCs and STP occur during the impact assembly. Rheological and kinetic analysis suggested the shear thinning behavior of the ChNCs liquid crystals and the rapid gelation phenomenon of ChNCs induced by STP. Morphology results showed that the rod-like ChNCs in the non-spherical assemblies were orderly and closely arranged with periodic repetition and layered structure. The non-spherical assemblies of ChNCs liquid crystals can be used as carriers of carbon nanotubes, magnetic Fe3O4 nanoparticles, synthesized polymers, and anticancer drugs for functional composite applications. The drop impact assembly method of ChNCs liquid crystal structure is highly controllable on the composition, morphology, and function, which shows promising applications in energy, environmental-friendly, and bioactive materials.

Ortho Effects of Tricarboxylate Linkers in Regulating Topologies of Rare-Earth Metal-Organic Frameworks.

A linker design strategy is developed to attain novel polynuclear rare-earth (RE) metal-organic frameworks (MOFs) with unprecedented topologies. We uncover the critical role of ortho-functionalized tricarboxylate ligands in directing the construction of highly connected RE MOFs. The acidity and conformation of the tricarboxylate linkers were altered by substituting with diverse functional groups at the ortho position of the carboxyl groups. For instance, the acidity difference between carboxylate moieties resulted in forming three hexanuclear RE MOFs with novel (3,3,3,10,10)-c wxl, (3,12)-c gmx, and (3,3,3,12)-c joe topologies, respectively. In addition, when a bulky methyl group was introduced, the incompatibility between the net topology and ligand conformation guided the co-appearance of hexanuclear and tetranuclear clusters, generating a novel 3-periodic MOF with a (3,3,8,10)-c kyw net. Interestingly, a fluoro-functionalized linker prompted the formation of two unusual trinuclear clusters and produced a MOF with a fascinating (3,8,10)-c lfg topology, which could be gradually replaced by a more stable tetranuclear MOF with a new (3,12)-c lee topology with extended reaction time. This work enriches the polynuclear clusters library of RE MOFs and unveils new opportunities to construct MOFs with unprecedented structural complexity and vast application potential.

High-performance flame-retardant aliphatic polyamide via enhanced chain entanglement

Although conventional chemical copolymerization method has shown favorable results in improving certain performance of polymers, simultaneous improvement of overall properties is hardly achieved. Here, we reported a feasible method to fabricate high-performance polymers with great overall properties by simultaneously tailoring their chemical constitution and topological conformation. We designed and synthesized a novel functional monomer with a sidechain caged structure based on phosphorus chemistry, and prepared the corresponding aliphatic polyamide as a typical representative of thermoplastic synthetic polymers. The incorporation of a sidechain caged structure enhanced the chain entanglement of the resultant polyamide, thus improved the mechanical strength by 39% and largely enhanced the heat resistance. The great processability was basically uninfluenced due to the easy dissociation of the entanglement during processing, enabling the potentially wide application fields as both fibers and engineering plastics. Furthermore, based on the free radical scavenging effect of the phosphorus-based monomer, the flame retardancy of the resultant polyamide was significantly improved. In sight of these findings, this work provides a novel method for fabricating high-performance polymers for various applications.

Ribbon‐Type Boron‐Doped Polycyclic Aromatic Hydrocarbons: Conformations, Dynamic Complexation and Electronic Properties

AbstractMolecular ribbons (MRs), one‐dimentional topological polycyclic aromatic hydrocarbons (PAHs), are of importance for synthetic chemistry and material sciences. Herein, we disclose an effective strategy to develop boron‐doped MRs, i.e. photochemical cyclization on conjugated organoboranes for rapid π‐extension. A series of ribbon‐type boron‐doped PAHs that own multiple cove edges were synthesized using Mallory photoreaction in solution. Two of them feature isomeric C68B2π‐skeletons with 2.2 nm in length, thus representing a new kind of boron‐doped MRs. The boron atoms endow them with sufficient Lewis acidity, and notably, the formed Lewis acid‐base adducts based on boron‐doped MRs display the photo‐induced dual‐dissociation behavior in the excited state and thus photochromism property. Moreover, despite of the highly contorted topological conformations, their potential utility as organic semiconductor was demonstrated by fabrication of organic field‐effect transistors.

Ribbon-Type Boron-Doped Polycyclic Aromatic Hydrocarbons: Conformations, Dynamic Complexation and Electronic Properties.

Molecular ribbons (MRs), one-dimentional topological polycyclic aromatic hydrocarbons (PAHs), are of importance for synthetic chemistry and material sciences. Herein, we disclose an effective strategy to develop boron-doped MRs, i.e. photochemical cyclization on conjugated organoboranes for rapid π-extension. A series of ribbon-type boron-doped PAHs that own multiple cove edges were synthesized using Mallory photoreaction in solution. Two of them feature isomeric C68 B2 π-skeletons with 2.2 nm in length, thus representing a new kind of boron-doped MRs. The boron atoms endow them with sufficient Lewis acidity, and notably, the formed Lewis acid-base adducts based on boron-doped MRs display the photo-induced dual-dissociation behavior in the excited state and thus photochromism property. Moreover, despite of the highly contorted topological conformations, their potential utility as organic semiconductor was demonstrated by fabrication of organic field-effect transistors.

The Local Topological Free Energy of the SARS-CoV-2 Spike Protein.

The novel coronavirus SARS-CoV-2 infects human cells using a mechanism that involves binding and structural rearrangement of its Spike protein. Understanding protein rearrangement and identifying specific amino acids where mutations affect protein rearrangement has attracted much attention for drug development. In this manuscript, we use a mathematical method to characterize the local topology/geometry of the SARS-CoV-2 Spike protein backbone. Our results show that local conformational changes in the FP, HR1, and CH domains are associated with global conformational changes in the RBD domain. The SARS-CoV-2 variants analyzed in this manuscript (alpha, beta, gamma, delta Mink, G614, N501) show differences in the local conformations of the FP, HR1, and CH domains as well. Finally, most mutations of concern are either in or in the vicinity of high local topological free energy conformations, suggesting that high local topological free energy conformations could be targets for mutations with significant impact of protein function. Namely, the residues 484, 570, 614, 796, and 969, which are present in variants of concern and are targeted as important in protein function, are predicted as such from our model.

Conformation-dominated surface antifouling and aqueous lubrication

Antifouling and aqueous lubrication are important properties for biomaterials, especially for those with implantation purposes. In order to better understand the polymer conformation dependence of the surface antifouling and lubrication properties, poly(ethylene glycol) (PEG) polymers with mono-functional and difunctional catechol anchors were designed and anchored on surface to adopt tail and loop conformations. Diblock and triblock copolymers with poly(dopamine methacrylamide) (PDMA) block as anchors and PEG block as the main body were synthesized and anchored on silicon surfaces by a "grafting to" strategy. The chemical composition, film thickness, and surface roughness of both coatings were controlled to be similar to give a direct comparison of looped brushes and tailed analogues. Then, the antifouling and surface friction behaviors were detected to verify the topological conformation effect of PEG polymer brushes. Results showed that PEG triblock copolymer modified surface exhibited an obviously better antifouling property and a lower friction coefficient of ∼0.011 than that of PEG diblock copolymer modified surface. Additionally, calculation and simulation results demonstrated that triblock copolymer had higher adsorption energy and anchored on surface with looped conformation. It is indicated that the strongly anchored PEG loops are effective for excellent antifouling and lubricating properties due to its strong hydration and steric hindrance. The conformation-dominated enhanced antifouling and reduced interfacial friction is an effective method for the development of excellent antifouling surfaces.

RecQ-helicase processing of G-rich DNA

The Werner syndrome ATP-dependent helicase (WRN) is part of the RecQ helicase family responsible for DNA maintenance. WRN's localization at telomeres during S-phase is enhanced upon replicative stress, and it is believed that WRN is responsible for resolving certain secondary DNA structures forming at telomeres and stalled replication forks. One of these structures is the G-quadruplex, which forms in guanine-rich DNA with various topological conformations, and might act as a roadblock for DNA maintenance proteins.

The local topological free energy of proteins

Protein folding, the process by which proteins attain a 3-dimensional conformation necessary for their function, remains an important unsolved problem in biology. A major gap in our understanding is how local properties of proteins relate to their global properties. In this manuscript, we use the Writhe and Torsion to introduce a new local topological/geometrical free energy that can be associated to 4 consecutive amino acids along the protein backbone. By analyzing a culled protein dataset from the PDB, our results show that high local topological free energy conformations are independent of sequence and may be involved in the rate limiting step in protein folding. By analyzing a set of 2-state single domain proteins, we find that the total local topological free energy of these proteins correlates with the experimentally observed folding rates reported in Plaxco et al. (2000).

Ligand-Directed Conformational Control over Porphyrinic Zirconium Metal-Organic Frameworks for Size-Selective Catalysis.

Zirconium-based metal-organic frameworks (Zr-MOFs) have aroused enormous interest owing to their superior stability, flexible structures, and intriguing functions. Precise control over their crystalline structures, including topological structures, porosity, composition, and conformation, constitutes an important challenge to realize the tailor-made functionalization. In this work, we developed a new Zr-MOF (PCN-625) with a csq topological net, which is similar to that of the well-known PCN-222 and NU-1000. However, the significant difference lies in the conformation of porphyrin rings, which are vertical to the pore surfaces rather than in parallel. The resulting PCN-625 exhibits two types of one-dimensional channels with concrete diameters of 2.03 and 0.43 nm. Furthermore, the vertical porphyrins together with shrunken pore sizes could limit the accessibility of substrates to active centers in the framework. On the basis of the structural characteristics, PCN-625(Fe) can be utilized as an efficient heterogeneous catalyst for the size-selective [4 + 2] hetero-Diels-Alder cycloaddition reaction. Due to its high chemical stability, this catalyst can be repeatedly used over six times. This work demonstrates that Zr-MOFs can serve as tailor-made scaffolds with enhanced flexibility for target-oriented functions.

Favorable formation of stereocomplex crystals in long-chain branched poly(L-lactic acid)/poly(D-lactic acid) blends: impacts of melt effect and molecular chain structure

A feasible approach is proposed to promote the formation of the stereocomplex crystal (Sc) in long-chain branched Poly(L-lactic acid)/Poly(D-lactic acid) (LCBPLA/PDLA) blends with hydrogen bond interactions. The synergistic effect of PDLA and long-chain branches significantly increases the crystalline ability of Sc from 20.1 to 30.4% due to the improved intermolecular crystal nucleation/growth. The frequency-independent loss tangent appeared at a PDLA concentration of 5.0 wt%, indicating a transition from the liquid-like to solid-like viscoelastic and the formation of a network composed of long-chain branches and the reserved Sc crystallites. Changing the processing temperatures from 190 to 230 °C seems to induce different melting behavior of Sc with diverse topological conformations so as to act as a template to attract PLLA molecule chains to perform the crystallization behavior. In situ wide-angle X-ray diffraction analysis reveals that a higher cooling temperature (less than 220 °C) significantly contributes to the Sc with more integrated structures and the Hc-to-Sc transition. The polarizing optical microscope results show that increasing the PDLA content and long-chain branched points significantly promote the spherulite growth and nuclei density of Sc, increasing the Sc size from 56.47 to 94.13 μm and nuclei density from 52.2 to 98.3%.

Synthesis, characterization, DNA binding and cytotoxicity studies of two novel Cu(II)-2-(2′-pyridyl) quinoxaline complexes

Two novel copper (II) complexes, namely [Cu(2,2′-pq)(NO3)](NO3) (1) and [Cu(2,2′-pq)2(NO3)](NO3)·6H2O(2) where 2,2′-pq is 2-(2′-pyridyl quinoxaline) were synthesized and characterized by various spectral methods. Complex 2 characterized by single crystal X-ray diffraction showed a distorted trigonal bipyramidal geometry and crystallized together with an hexamer, (H2O)6 cluster, with R66(12) topology and chair conformation. The interaction of Calf Thymus DNA (CT-DNA) with 1 and 2 was investigated by UV–Visible absorption spectra, Viscosity, Cyclic Voltammetry, Fluorescence and Circular Dichroism (CD), indicating that both complexes can bind to DNA both by means of intercalation and groove binding. Their DNA interaction mode depends on their concentrations and the differences between their structures. Cleavage experiments were performed by agarose gel electrophoresis using pBR322 DNA both in dark and after illumination. Furthermore, the cytotoxicity of both complexes was evaluated against MCF-7 and healthy cells (HEK-293) by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays; moreover their cell uptake against MCF-7 tumor cells and HEK-293 normal cells was revealed by using confocal laser scanning. Both complexes have the potential to act as effective anticancer drugs with 2 to present an IC50 smaller than that of cis-platin and also to be useful for optically probing tumor cells since it fluoresces at blue and green when is treated with MCF-7 cells.

Ordered aggregation structures of semiflexible ring polymers in ring-linear blends

Conformations and dynamical properties of semiflexible ring polymers (SRPs) in semiflexible ring-linear blends are investigated by using molecular dynamic simulation. The conformations of SRPs rely mainly on bending energy (Kb,linear) and chain length (Nlinear) of semiflexible linear polymers as well as the fraction of SRPs (φring) in semiflexible ring-linear blends. SRPs are randomly immersed in flexible or short semiflexible linear polymer melts, however, ordered aggregation structures of SRPs are formed in the matrix of semiflexible linear polymers, especially for long semiflexible linear polymers. These ordered aggregation structures are induced by entropy of SRPs, and long semiflexible linear polymers can improve the overlap of SRPs in semiflexible ring-linear blends. In addition, the center-of-mass diffusion coefficient (D) of SRPs first decreases abruptly and then gradually with the bending energy of linear polymers increasing in semiflexible ring-linear blends, and SRPs diffuse very slowly in the blends of long semiflexible linear polymers due to the strong threading by long semiflexible linear polymers. Our results may help us understand special topological conformations and dynamical behaviors of SRPs in semiflexible ring-linear blends.

Lipid-Assisted Membrane Protein Folding and Topogenesis.

Due to the heterogenous lipid environment in which integral membrane proteins are embedded, they should follow a set of assembly rules, which govern transmembrane protein folding and topogenesis accordingly to a given lipid profile. Recombinant strains of bacteria have been engineered to have different membrane phospholipid compositions by molecular genetic manipulation of endogenous and foreign genes encoding lipid biosynthetic enzymes. Such strains provide a means to investigate the in vivo role of lipids in many different aspects of membrane function, folding and biogenesis. In vitro and in vivo studies established a function of lipids as molecular chaperones and topological determinants specifically assisting folding and topogenesis of membrane proteins. These results led to the extension of the Positive Inside Rule to Charge Balance Rule, which incorporates a role for lipid-protein interactions in determining membrane protein topological organization at the time of initial membrane insertion and dynamically after initial assembly. Membrane protein topogenesis appears to be a thermodynamically driven process in which lipid-protein interactions affect the potency of charged amino acid residues as topological signals. Dual topology for a membrane protein can be established during initial assembly where folding intermediates in multiple topological conformations are in rapid equilibrium (thus separated by a low activation energy), which is determined by the lipid environment. Post-assembly changes in lipid composition or post-translational modifications can trigger a reorganization of protein topology by inducing destabilization and refolding of a membrane protein. The lipid-dependent dynamic nature of membrane protein organization provides a novel means of regulating protein function.

The Deep Sea Osmolyte TrimethylamineN‐Oxide and Macromolecular Crowders Rescue the Antiparallel Conformation of the Human Telomeric G‐Quadruplex from Urea and Pressure Stress

Organisms are thriving in the deep sea at pressures up to the 1 kbar level, which imposes severe stress on the conformational dynamics and stability of their biomolecules. The impact of osmolytes and macromolecular crowders, mimicking intracellular conditions, on the effect of pressure on the conformational dynamics of a human telomeric G-quadruplex (G4) DNA is explored in this study employing single-molecule Förster resonance energy transfer (FRET) experiments. In neat buffer, pressurization favors the parallel/hybrid state of the G4-DNA over the antiparallel conformation at ≈400 bar, finally leading to unfolding beyond 1000 bar. High-pressure NMR data support these findings. The folded topological conformers have different solvent accessible surface areas and cavity volumes, leading to different volumetric properties and hence pressure stabilities. The deep-sea osmolyte trimethylamine N-oxide (TMAO) and macromolecular crowding agents are able to effectively rescue the G4-DNA from unfolding in the whole pressure range encountered on Earth.