Structure-function Relationships Research Articles

G × E × M analysis to define allometric rules between leaves and stems in wheat.

Allometric rules provide insights into the structure-function relationships across species and scales and are commonly used in ecology. The fields of agronomy, plant phenotyping and modeling also need simplifications such as allometric rules to reconcile data at different temporal and spatial levels (organs/canopy). This paper explores the variations in relationships for wheat regarding (i) the distribution of crop green area between leaves and stems, and (ii) the allocation of above-ground biomass between leaves and stems during the vegetative period, using a large dataset covering different years, countries, genotypes and management practices. Our results show that the relationship between leaf and stem area was linear, genotype-specific, and sensitive to radiation. The relationship between leaf and stem biomass depended on genotype and nitrogen fertilization. The mass per area, associating area and biomass for both leaf and stem, varied strongly by developmental stage and was significantly affected by environment and genotype. These allometric rules were evaluated with satisfactory performance, and their potential use is discussed with regard to current phenotyping techniques and plant/crop models. Our results enable the definition of models and minimum datasets required for characterizing diversity panels and making predictions in various G × E × M contexts.

Structure-based investigation of a DNA aptamer targeting PTK7 reveals an intricate 3D fold guiding functional optimization

DNA aptamers have emerged as novel molecular tools in disease theranostics owing to their high binding affinity and specificity for protein targets, which rely on their ability to fold into distinctive three-dimensional (3D) structures. However, delicate atomic interactions that shape the 3D structures are often ignored when designing and modeling aptamers, leading to inefficient functional optimization. Challenges persist in determining high-resolution aptamer-protein complex structures. Moreover, the experimentally determined 3D structures of DNA molecules with exquisite functions remain scarce. These factors impede our comprehension and optimization of some important DNA aptamers. Here, we performed a streamlined solution NMR-based structural investigation on the 41-nt sgc8c, a prominent DNA aptamer used to target membrane protein tyrosine kinase 7, for cancer theranostics. We show that sgc8c prefolds into an intricate three-way junction (3WJ) structure stabilized by long-range tertiary interactions and extensive base-base stackings. Delineated by NMR chemical shift perturbations, site-directed mutagenesis, and 3D structural information, we identified essential nucleotides constituting the key functional elements of sgc8c that are centralized at the core of 3WJ. Leveraging the well-established structure-function relationship, we efficiently engineered two sgc8c variants by modifying the apical loop and introducing L-DNA base pairs to simultaneously enhance thermostability, biostability, and binding affinity for both protein and cell targets, a feat not previously attained despite extensive efforts. This work showcases a simplified NMR-based approach to comprehend and optimize sgc8c without acquiring the complex structure, and offers principles for the sophisticated structure-function organization of DNA molecules.

Rutile TiO2-Supported Pt Nanoparticle Catalysts for the Low-Temperature Oxidation of Ethane to Ethanol.

Structure-function relationships of supported metal nanoparticle catalysts in the CO-assisted oxidation of ethane to ethanol were investigated. A rutile TiO2-supported Pt nanoparticle catalyst exhibited the highest ethanol production rate and selectivity. During the reaction, sequential changes in the geometric/electronic states and the particle size of the Pt nanoparticles were observed. The comparison of the catalytic performances of model catalysts with controlled metal-support interactions revealed that Pt0 nanoparticles of 2-3 nm with a high fraction of the surface Ptδ+ species are highly active for the oxidation of ethane to ethanol. The coadded CO plays a pivotal role not only in tuning the oxidation state of the surface Pt but also in producing H2O2, which is the true oxidant for the reaction. The supported Pt nanoparticle uses in situ-generated H2O2 to activate ethane, where the C2H5OOH intermediate is formed through a nonradical mechanism and subsequently converted to C2H5OH. This reaction occurs even at 50 °C with an apparent activation energy of 32 kJ mol-1. The present study sheds light on the usefulness of surface-engineered Pt nanoparticles for the low-temperature oxidation of ethane to ethanol.

Electron-Withdrawing Substituents Enhance the Type I PDT and NIR-II Fluorescence of BODIPY J Aggregates for Bioimaging and Cancer Therapy.

Organic dyes with simultaneously boosted near-infrared-II (NIR-II) fluorescence, type I photodynamic therapy (PDT), and photothermal therapy (PTT) in the aggregate state are still elusive due to the unclear structure-function relationship. Herein, electron-withdrawing substituents are introduced at the 5-indolyl positions of BODIPY dyes to form tight J-aggregates for enhanced NIR-II fluorescence and type I PDT/PTT. The introduction of an electron-rich julolidine group at the meso position and an electron-withdrawing substituent (-F) at the indolyl moiety can enhance intermolecular charge transfer and the hydrogen bonding effect, contributing to the efficient generation of superoxide radicals in the aggregate state. The nanoparticles of BDP-F exhibit NIR-II fluorescence at 1000 nm, good superoxide radical generation ability, and a high photothermal conversion efficiency (50.9%), which enabled NIR-II fluorescence-guided vasculature/tumor imaging and additive PDT/PTT. This work provides a strategy for constructing phototheranostic agents with enhanced NIR-II fluorescence and type I PDT/PTT for broad biomedical applications.

A vitamin D-based strategy overcomes chemoresistance in prostate cancer.

Castration-resistant prostate cancer (CRPC) is a common male malignancy that requires new therapeutic strategies due to acquired resistance to its first-line treatment, docetaxel. The benefits of vitamin D on prostate cancer (PCa) progression have been previously reported. This study aimed to investigate the effects of vitamin D on chemoresistance in CRPC. Structure function relationships of potent vitamin D analogues were determined. The combination of the most potent analogue and docetaxel was explored in chemoresistant primary PCa spheroids and in a xenograft mouse model derived from a patient with a chemoresistant CRPC. Here, we show that Xe4MeCF3 is more potent than the natural ligand to induce vitamin D receptor (VDR) transcriptional activities and that it has a larger therapeutic window. Moreover, we demonstrate that VDR agonists restore docetaxel sensitivity in PCa spheroids. Importantly, Xe4MeCF3 reduces tumour growth in a chemoresistant CRPC patient-derived xenograft. In addition, this treatment targets signalling pathways associated with cancer progression in the remaining cells. Taken together, these results unravel the potency of VDR agonists to overcome chemoresistance in CRPC and open new avenues for the clinical management of PCa.

Deciphering the Thermal Stability of Bacteriophage MS2-Derived Virus-like Particle and Its Engineered Variant.

RNA bacteriophage MS2-derived virus-like particles (VLPs) have been widely used in biomedical research as model systems to study virus assembly, structure-function relationships, vaccine development, and drug delivery. Considering the diverse utility of these VLPs, a systemic engineering approach has been utilized to generate smaller particles with optimal serum stability and tissue penetrance. Additionally, it is crucial to demonstrate the overall stability of these mini MS2 VLPs, ensuring cargo protection until they reach their target cell/organ. However, no detailed analysis of the thermal stability and heat-induced disassembly of MS2 VLPs has yet been attempted. In this work, we investigated the thermal stability of both wild-type (WT) MS2 VLP and its "mini" variant containing S37P mutation (mini MS2 VLP). The mini MS2 VLP exhibits a higher capsid melting temperature (Tm) when compared to its WT MS2 VLP counterpart, possibly attributed to its smaller interdimer angle. Our study presents that the thermal unfolding of MS2 VLPs follows a sequential process involving particle destabilization, nucleic acid exposure/melting, and disassembly of VLP. This observation underscores the disruption of cooperative intersubunit interactions and protein-nucleic acid interactions, shedding light on the mechanism of heat-induced VLP disassembly.

Ligand–Receptor Interactions and Structure–Function Relationships in Off-Target Binding of the β3-Adrenergic Agonist Mirabegron to α1A-Adrenergic Receptors

The β3-adrenoceptor agonist mirabegron is available for the treatment of storage symptoms of overactive bladder, including frequency, urgency, and incontinence. The off-target effects of mirabegron include binding to α1-adrenoceptors, which are central in the treatment of voiding symptoms. Here, we examined the structure–function relationships in the binding of mirabegron to a cryo-electron microscopy structure of α1A. The binding was simulated by docking mirabegron to a 3D structure of a human α1A-adrenoceptor (7YMH) using Autodock Vina. The simulations identified two binding states: slope orientation involving 10 positions and horizontal binding to the receptor surface involving 4 positions. No interactions occurred with positions constituting the α1A binding pocket, including Asp-106, Ser-188, or Phe-312, despite the positioning of the phenylethanolamine moiety in transmembrane regions close to the binding pocket by contact with Phe-288, -289, and Val-107. Contact with the unique positions of α1A included the transmembrane Met-292 during slope binding and exosite Phe-86 during horizontal binding. Exosite binding in slope orientation involved contact of the anilino part, rather than the aminothiazol end, to Ile-178, Ala-103, and Asn-179. In conclusion, contact with Met-292 and Phe-86, which are unique positions of α1A, accounts for mirabegron binding to α1A. Because of its lack of interactions with the binding pocket, mirabegron has lower affinity compared to α1A-blockers and no effects on voiding symptoms.

Arginine-Rich Peptide-Rhodium Nanocluster@Reduced Graphene Oxide Composite as a Highly Selective and Active Uricase-like Nanozyme for the Degradation of Uric Acid and Inhibition of Urate Crystal.

Metal nanozymes have offered attractive opportunities for biocatalysis and biomedicine. However, fabricating nanozymes simultaneously possessing highly catalytic selectivity and activity remains a great challenge due to the lack of three-dimensional (3D) architecture of the catalytic pocket in natural enzymes. Here, we integrate rhodium nanocluster (RhNC), reduced graphene oxide (rGO), and protamine (PRTM, a typical arginine-rich peptide) into a composite facilely based on the single peptide. Remarkably, the PRTM-RhNC@rGO composite displays outstanding selectivity, activity, and stability for the catalytic degradation of uric acid. The reaction rate constant of the uric acid oxidation catalyzed by the PRTM-RhNC@rGO composite is about 1.88 × 10-3 s-1 (4 μg/mL), which is 37.6 times higher than that of reported RhNP (k = 5 × 10-5 s-1, 20 μg/mL). Enzyme kinetic studies reveal that the PRTM-RhNC@rGO composite exhibits a similar affinity for uric acid as natural uricase. Furthermore, the uricase-like activity of PRTM-RhNC@rGO nanozymes remains in the presence of sulfur substances and halide ions, displaying incredibly well antipoisoning abilities. The analysis of the structure-function relationship indicates the PRTM-RhNC@rGO composite features the substrate binding site near the catalytic site in a confined space contributed by 2D rGO and PRTM, resulting in the high-performance of the composite nanozyme. Based on the outstanding uricase-like activity and the interaction of PRTM and uric acid, the PRTM-RhNC@rGO composite can retard the urate crystallization significantly. The present work provides new insights into the design of metal nanozymes with suitable binding sites near catalytic sites by mimicking pocket-like structures in natural enzymes based on simple peptides, conducing to broadening the practical application of high-performance nanozymes in biomedical fields.

Anti-virus activity and mechanisms of natural polysaccharides from medicinal herbs

There has been a sudden increase in viral diseases, such as coronavirus disease 2019 (COVID-19), causing significant harm to human and animal well-being, as well as economic development. Medicinal herbs, with a history of thousands of years in clinical use, contain versatile polysaccharides as one of their primary compounds. This review offers an overview of the antiviral effects of polysaccharides from medicinal herbs on viruses in humans, poultry, swine and aquaculture in recent years. The mechanism of these antiviral polysaccharides, involved in hindering various stages of the viral life cycle thereby blocking virus infection, is summarized. The review also explores other underlying mechanisms of antiviral effects, such as enhancing the immune response, regulating inflammatory reactions, balancing gut flora, reducing oxidative stress, and suppressing apoptosis through various corresponding signaling pathways. The structure-function relationships discussed in this article also aid in understanding the antiviral mechanism of natural polysaccharides, indicating the need for more in-depth research and analysis. Natural polysaccharides from medicinal herbs have emerged as valuable resources in the fight against viral infections, exhibiting high effectiveness. This review emphasizes the promising role of polysaccharides from medicinal herbs as potential candidates for blocking viral infections in humans and animals.

Liver-specific delivery of spherical DNA frameworks for alleviation of hepatic ischemic reperfusion injury

DNA nanostructures have long been developed for biomedical purposes, but their controlled delivery in vivo proposes a major challenge for disease theranostics. We previously reported that DNA nanostructures on the scales of tens and hundreds nanometers showed preferential renal excretion or kidney retention, allowing for sensitive evaluation and effective protection of kidney function, in response to events such as unilateral ureter obstruction or acute kidney injury. Encouraged by the positive results, we redirected our focus to the liver, specifically targeting organs noticeably lacking DNA materials, to explore the interaction between DNA nanostructures and the liver. Through PET imaging, we identified SDF and M13 as DNA nanostructures exhibiting significant accumulation in the liver among numerous candidates. Initially, we investigated and assessed their biodistribution, toxicity, and immunogenicity in healthy mice, establishing the structure-function relationship of DNA nanostructures in the normal murine. Subsequently, we employed a mouse model of liver ischemia-reperfusion injury (IRI) to validate the nano-bio interactions of SDF and M13 under more challenging pathological conditions. M13 not only exacerbated hepatic oxidative injury but also elevated local apoptosis levels. In contrast, SDF demonstrated remarkable ability to scavenge oxidative responses in the liver, thereby mitigating hepatocyte injury. These compelling results underscore the potential of SDF as a promising therapeutic agent for liver-related conditions. This aimed to elucidate their roles and mechanisms in liver injury, providing a new perspective for the biomedical applications of DNA nanostructures.Graphical Spherical DNA framework showed predominant liver retention to rescue hepatic 870 ischemia reperfusion injury

Dependence of the formation kinetics of carbon dioxide hydrate on clay aging for solid carbon dioxide storage

Clay-based marine sediments have great potential for safe and effective carbon dioxide (CO2) encapsulation by storing enormous amounts of CO2 in solid gas hydrate form. However, the aging of clay with time changes the surface properties of clay and complicates the CO2 hydrate formation behaviors in sediments. Due to the long clay aging period, it is difficult to identify the role of clay aging in the formation of CO2 hydrate in marine sediments. Here, we used ultrasonication and plasma treatment to simulate the breakage and oxidation of clay nanoflakes in aging and investigated the influence of clay aging on CO2 hydrate formation kinetics. We found that the breakage and oxidation of clay nanoflakes would disrupt the siloxane rings and graft hydroxyl on the clay nanoflakes. This decreased the negative charge density of clay nanoflakes and weakened the interfacial interaction of clay nanoflakes with the surrounding water. Therefore, the small clay nanoflakes enriched in hydroxyl would disrupt the surrounding tetrahedral water structure analogous to the CO2 hydrate, resulting in the prolongation of CO2 hydrate nucleation. These results revealed the influence of the structure-function relationship of clay nanoflakes with CO2 hydrate formation and are favorable for the development of hydrate-based CO2 storage.

Tertiary phosphine‐supported diiron model complexes relevant to [FeFe]‐hydrogenases

In an effort to better probe the structure–function relationship on the biological [Fe4S4] cluster of [FeFe]‐hydrogenases, a new library of tertiary phosphine‐supported diiron dithiolate complexes [Fe2(μ‐adtNR)(CO)5{P(C6H4X)3}] (1–3) with various substituents (X = F vs. H vs. Me), wherein adtNR is denoted as abbreviation for the (SCH2)2N(C6H4C2H4OC(O)CH2C6H4Me) unit, is prepared as the active site mimics of [FeFe]‐hydrogenases. Notably, the substituent influences of tertiary phosphines on the structures and electrochemical behaviors of 1–3 are studied by spectroscopic and crystallographic techniques as well as cyclic voltammetry. For example, the electronic effect of tertiary phosphines [P(C6H4X)3] is responsible for the electron density around diiron center and the key Fe–Fe as well as Fe–P lengths in 1–3 as revealed by IR spectroscopy and crystallographic analysis. Further, complexes 1–3 show the electrochemical activity for proton reduction into molecular hydrogen (H2) using acetic acid (AcOH) as a proton source. Noticeably, F‐substituent‐containing diiron model complex 1 exhibits greater turnover frequency (i.e., turnover frequency value) and similar overpotential for electrocatalytic H2 evolution relative to H‐ or Me‐substituent‐bearing diiron homologs 2 or 3.

International Union of Basic and Clinical Pharmacology. CXV: The Class F of G Protein-Coupled Receptors.

The class F of G protein-coupled receptors (GPCRs) consists of ten Frizzleds (FZD1-10) and Smoothened (SMO). FZDs bind and are activated by secreted lipoglycoproteins of the Wingless/Int-1 (WNT) family and SMO is indirectly activated by the Hedgehog (Hh) family of morphogens acting on the transmembrane protein Patched (PTCH). The advance of our understanding of FZDs and SMO as dynamic transmembrane receptors and molecular machines, which emerged during the past 14 years since the first class F GPCR IUPHAR nomenclature report, justifies an update. This article focuses on the advances in molecular pharmacology and structural biology providing new mechanistic insight into ligand recognition, receptor activation mechanisms, signal initiation and signal specification. Furthermore, class F GPCRs continue to develop as drug targets, and novel technologies and tools such as genetically encoded biosensors and CRISP/Cas9 edited cell systems have contributed to refined functional analysis of these receptors. Also, advances in crystal structure analysis and cryogenic electron microscopy contribute to a rapid development of our knowledge about structure-function relationships providing a great starting point for drug development. Despite the progress questions and challenges remain to fully understand the complexity of the WNT/FZD and Hh/SMO signaling systems. Significance Statement The recent years of research have brought about substantial functional and structural insight into mechanisms of activation of Frizzleds and Smoothened. While the advance furthers our mechanistic understanding of ligand recognition, receptor activation, signal specification and initiation, broader opportunities emerge that allow targeting class F GPCRs for therapy and regenerative medicine employing both biologics and small molecule compounds.

3D-printed Ti6Al4V thoracic fusion cage: Biomechanical behavior and strengthening mechanism

To effectively replace diseased and damaged thoracic vertebrae, a series of three-dimensional (3D) printed titanium (Ti) alloy (Ti6Al4V) thoracic fusion cages with varying volume ratio of reinforced scaffolds are designed, and their structure-function relationships are investigated systematically. It is demonstrated that the mechanical strength of fusion cage is gradually enhanced as the scaffold volume increases, which may be attributed to its textural transformation from α phase to β phase. The compressive, shear, and fatigue of fusion cages successfully attain the International Organization for Standardization (ISO 23089), when the scaffold volume ratio exceeds 15%. Furthermore, the biomechanical analyses, including stress distributions and subsidence in flexion, extension, axial rotation, and lateral bending sections of fusion cages, further shed light on their potential clinical applications. This work deeply deciphers the intrinsic connection between biomechanical property and material texture of the thoracic fusion cages, offering valuable insights into their strengthening mechanism, which providing a guidance for the precise design and quick synthesis of other 3D-printed Ti6Al4V implants.

Three anti-inflammatory polysaccharides from Lonicera japonica Thunb.: Insights into the structure-function relationships

This study demonstrates the feasibility of producing three polysaccharides (neutral LJP-1, acidic LJP-2 and acidic LJP-3) with significant in vitro and in vivo anti-inflammatory activities from the flowers of Lonicera japonica. The three polysaccharides differed in chemical composition, molecular weight distribution, glycosidic linkage pattern, functional groups and morphology. They exhibited excellent protective effects (in a dose-dependent manner) in lipopolysaccharide-injured RAW264.7 macrophages and CuSO4-damaged zebrafish via reducing NO production and inhibiting the overexpressions of inflammation-related transcription factors, inflammatory proteins and cytokines in the NF-κB/MAPK signaling pathways. Their anti-inflammatory effects varied owing to their different molecular characteristics and chemical compositions. Overall, LJP-2 at 400μg/mL was the most effective. LJP-2 consisted mainly of → 5)-α-L-Araf (1→, →4)-α-L-GalpA (1→ and →2)-α-L-Rhap (1→ residues with terminal T-β-D-Glcp. Thus, honeysuckle flowers are good sources of anti-inflammatory polysaccharides, and precise fractionation enables the production of potent anti-inflammatory agents for the development of functional foods and healthcare products.

Development of Novel Protein-Rich Foods: Studies of Composite Hydrogels Formed from Potato Proteins and Gellan Gums with Different Degrees of Acylation

The textural attributes of mixed hydrogels formed from potato protein (PP) and gellan gum (GG) were examined for their potential application as novel protein-rich foods (NPFs). Initially, the properties of gels formed by the individual biopolymers were characterized using dynamic shear rheology, compression testing, and confocal fluorescence microscopy. Rheological analysis revealed that PP dispersions formed irreversible heat-set gels, whereas GG formed reversible cold-set gels at lower temperatures. The effects of adding PP to high acyl gellan gum (HA-GG) or low acyl gellan gum (LA-GG) solutions on the microstructure and rheology of the mixed gels formed were then examined. The PP/LA-GG composite gels had a highly heterogeneous microstructure consisting of protein-rich and polysaccharide-rich regions. In contrast, the PP/HA-GG composite gels had a more uniform microstructure. Interestingly, the incorporation of the PP weakened the PP/LA-GG composite gels (antagonism) but strengthened the PP/HA-GG composite gels (synergism), which was mainly attributed to their different impacts on gel microstructure. This study shows that semi-solid plant protein-dietary fiber composites can be formed with a variety of textural attributes by altering the nature and concentration of biopolymers used to formulate them. These mixed gels may be useful for the creation of NPFs. This study also highlights the complexity of the interactions between different food biopolymers and their impacts on food properties, highlighting the need for further research on understanding structure-function relationships in multicomponent biopolymer materials.

Effects of packetization on communication dynamics in brain networks

Abstract Computational studies in network neuroscience build models of communication dynamics in the connectome that help us understand the structure-function relationships of the brain. In these models, the dynamics of cortical signal transmission in brain networks are approximated with simple propagation strategies such as random walks and shortest path routing. Furthermore, the signal transmission dynamics in brain networks can be associated with the switching architectures of engineered communication systems (e.g., message switching and packet switching). However, it has been unclear how propagation strategies and switching architectures are related in models of brain network communication. Here, we investigate the effects of the difference between packet switching and message switching (i.e., whether signals are packetized or not) on the transmission completion time of propagation strategies when simulating signal propagation in mammalian brain networks. The results show that packetization in the connectome with hubs increases the time of the random walk strategy and does not change that of the shortest path strategy, but decreases that of more plausible strategies for brain networks that balance between communication speed and information requirements. This finding suggests an advantage of packet-switched communication in the connectome and provides new insights into modeling the communication dynamics in brain networks.

S100A1's single cysteine is an indispensable redox switch for the protection against diastolic calcium waves in cardiomyocytes.

The EF-hand calcium (Ca2+) sensor protein S100A1 combines inotropic with antiarrhythmic potency in cardiomyocytes (CMs). Oxidative posttranslational modification (ox-PTM) of S100A1's conserved, single-cysteine residue (C85) via reactive nitrogen species (i.e., S-nitrosylation or S-glutathionylation) has been proposed to modulate conformational flexibility of intrinsically disordered sequence fragments and to increase the molecule's affinity toward Ca2+. Considering the unknown biological functional consequence, we aimed to determine the impact of the C85 moiety of S100A1 as a potential redox switch. We first uncovered that S100A1 is endogenously glutathionylated in the adult heart in vivo. To prevent glutathionylation of S100A1, we generated S100A1 variants that were unresponsive to ox-PTMs. Overexpression of wild-type (WT) and C85-deficient S100A1 protein variants in isolated CM demonstrated equal inotropic potency, as shown by equally augmented Ca2+ transient amplitudes under basal conditions and β-adrenergic receptor (βAR) stimulation. However, in contrast, ox-PTM defective S100A1 variants failed to protect against arrhythmogenic diastolic sarcoplasmic reticulum (SR) Ca2+ waves and ryanodine receptor 2 (RyR2) hypernitrosylation during βAR stimulation. Despite diastolic performance failure, C85-deficient S100A1 protein variants exerted similar Ca2+-dependent interaction with the RyR2 than WT-S100A1. Dissecting S100A1's molecular structure-function relationship, our data indicate for the first time that the conserved C85 residue potentially acts as a redox switch that is indispensable for S100A1's antiarrhythmic but not its inotropic potency in CMs. We, therefore, propose a model where C85's ox-PTM determines S100A1's ability to beneficially control diastolic but not systolic RyR2 activity.NEW & NOTEWORTHY S100A1 is an emerging candidate for future gene-therapy treatment of human chronic heart failure. We aimed to study the significance of the conserved single-cysteine 85 (C85) residue in cardiomyocytes. We show that S100A1 is endogenously glutathionylated in the heart and demonstrate that this is dispensable to increase systolic Ca2+ transients, but indispensable for mediating S100A1's protection against sarcoplasmic reticulum (SR) Ca2+ waves, which was dependent on the ryanodine receptor 2 (RyR2) nitrosylation status.

Applying Machine Learning to Design Delicate Amorphous Micro-Nano Materials for Rechargeable Batteries

As modern society evolves, the global importance of energy requirements has grown significantly. Thus, exploring new materials for renewable energy storage is urgently needed. Due to its intriguing characteristics, amorphous micro-nanomaterials demonstrate exceptional performance in energy storage. The long experimental periods and high costs associated with traditional methods make it challenging to meet the requirements of materials science. Currently, machine learning (ML) is emerging as a novel research paradigm with the potential to revolutionize the exploration of materials. This review provides an overview of the application of ML in studying amorphous micro-nanomaterials for rechargeable batteries. First, a comprehensive introduction to the fundamentals of amorphous materials and ML is summarized. Then, we highlight a series of representative works to elaborate the relationship between the ML for amorphous nanomaterials. Finally, an insightful perspective on utilization of amorphous materials to establish mature energy storage systems and future directions in ML for amorphous materials are presented. Through this review, we aim to unveil the underlying amorphous structure-function relationship and fuel further research in the design of amorphous materials with outstanding performance across diverse fields.

Sampling Conformational Ensembles of Highly Dynamic Proteins via Generative Deep Learning.

Proteins are inherently dynamic, and their conformational ensembles are functionally important in biology. Large-scale motions may govern protein structure-function relationship, and numerous transient but stable conformations of intrinsically disordered proteins (IDPs) can play a crucial role in biological function. Investigating conformational ensembles to understand regulations and disease-related aggregations of IDPs is challenging both experimentally and computationally. In this paper we first introduced an unsupervised deep learning-based model, termed Internal Coordinate Net (ICoN), which learns the physical principles of conformational changes from molecular dynamics (MD) simulation data. Second, we selected interpolating data points in the learned latent space that rapidly identify novel synthetic conformations with sophisticated and large-scale sidechains and backbone arrangements. Third, with the highly dynamic amyloid-β 1-42 (Aβ42) monomer, our deep learning model provided a comprehensive sampling of Aβ42's conformational landscape. Analysis of these synthetic conformations revealed conformational clusters that can be used to rationalize experimental findings. Additionally, the method can identify novel conformations with important interactions in atomistic details that are not included in the training data. New synthetic conformations showed distinct sidechain rearrangements that are probed by our EPR and amino acid substitution studies. This approach is highly transferable and can be used for any available data for training. The work also demonstrated the ability for deep learning to utilize learned natural atomistic motions in protein conformation sampling.