Background:Triple-negative breast cancer(TNBC),characterized by its lack of traditional hormone receptors and HER2,presents a significant challenge in oncology due to its poor response to conventional therapies.Autoph...Background:Triple-negative breast cancer(TNBC),characterized by its lack of traditional hormone receptors and HER2,presents a significant challenge in oncology due to its poor response to conventional therapies.Autophagy is an important process for maintaining cellular homeostasis,and there are currently autophagy biomarkers that play an effective role in the clinical treatment of tumors.In contrast to targeting protein activity,intervention with proteinprotein interaction(PPI)can avoid unrelated crosstalk and regulate the autophagy process with minimal interference pathways.Methods:Here,we employed Naive Bayes,Decision Tree,and k-Nearest Neighbors to elucidate the complex PPI network associated with autophagy in TNBC,aiming to uncover novel therapeutic targets.Meanwhile,the candidate proteins interacting with Beclin 2 were initially screened in MDA-MB-231 cells using Beclin 2 as bait protein by immunoprecipitation-mass spectrometry assay,and the interaction relationship was verified by molecular docking and CO-IP experiments after intersection.Colony formation,cellular immunofluorescence,cell scratch and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)tests were used to predict the clinical therapeutic effects of manipulating candidate PPI.Results:By developing three PPI classification models and analyzing over 13,000 datasets,we identified 3733 previously unknown autophagy-related PPIs.Our network analysis revealed the central role of Beclin 2 in autophagy regulation,uncovering its interactions with 39 newly identified proteins.Notably,the CO-IP studies identified the substantial interaction between Beclin 2 and Ubiquilin 1,which was anticipated by our model and discovered in immunoprecipitation-mass spectrometry assay results.Subsequently,in vitro investigations showed that overexpressing Beclin 2 increased Ubiquilin 1,promoted autophagy-dependent cell death,and inhibited proliferation and metastasis in MDA-MB-231 cells.Conclusions:This study not only enhances our understanding of autophagy regulation in TNBC but also identifies the Beclin 2-Ubiquilin 1 axis as a promising target for precision therapy.These findings open new avenues for drug discovery and offer inspiration for more effective treatments for this aggressive cancer subtype.展开更多
Almost all the cellular processes in a living system are controlled by proteins:They regulate gene expression,catalyze chemical reactions,transport small molecules across membranes,and transmit signal across membranes...Almost all the cellular processes in a living system are controlled by proteins:They regulate gene expression,catalyze chemical reactions,transport small molecules across membranes,and transmit signal across membranes.Even,a viral infection is often initiated through virus-host protein interactions.Protein-protein interactions(PPIs)are the physical contacts between two or more proteins and they represent complex biological functions.Nowadays,PPIs have been used to construct PPI networks to study complex pathways for revealing the functions of unknown proteins.Scientists have used PPIs to find the molecular basis of certain diseases and also some potential drug targets.In this review,we will discuss how PPI networks are essential to understand the molecular basis of virus-host relationships and several databases which are dedicated to virus-host interaction studies.Here,we present a short but comprehensive review on PPIs,including the experimental and computational methods of finding PPIs,the databases dedicated to virus-host PPIs,and the associated various applications in protein interaction networks of some lethal viruses with their hosts.展开更多
Neurological and neuropsychiatric disorders are one of the leading causes of disability worldwide and affect the health of billions of people.Nitric oxide(NO),a free gas with multitudinous bioactivities,is mainly prod...Neurological and neuropsychiatric disorders are one of the leading causes of disability worldwide and affect the health of billions of people.Nitric oxide(NO),a free gas with multitudinous bioactivities,is mainly produced from the oxidation of L-arginine by neuronal nitric oxide synthase(nNOS)in the brain.Inhibiting nNOS benefits a variety of neurological and neuropsychiatric disorders,including stroke,depression and anxiety disorders,posttraumatic stress disorder,Parkinson’s disease,Alzheimer’s disease,chronic pain,and drug addiction.Due to critical roles of nNOS in learning and memory and synaptic plasticity,direct inhibition of nNOS may cause severe side effects.Importantly,interactions of several proteins,including post-synaptic density 95(PSD-95),carboxyterminal PDZ ligand of nNOS(CAPON)and serotonin transporter(SERT),with the PSD/Disc-large/ZO-1 homologous(PDZ)domain of nNOS have been demonstrated to influence the subcellular distribution and activity of the enzyme in the brain.Therefore,it will be a preferable means to interfere with nNOS-mediated proteinprotein interactions(PPIs),which do not lead to undesirable effects.Herein,we summarize the current literatures on nNOS-mediated PPIs involved in neurological and neuropsychiatric disorders,and the discovery of drugs targeting the PPIs,which is expected to provide potential targets for developing novel drugs and new strategy for the treatment of neurological and neuropsychiatric disorders.展开更多
Protein-protein interactions(PPIs) are recognized as attractive therapeutic targets. However targeting PPIs especially intracellular ones has been proven extremely difficult for conventional drug-like small molecules,...Protein-protein interactions(PPIs) are recognized as attractive therapeutic targets. However targeting PPIs especially intracellular ones has been proven extremely difficult for conventional drug-like small molecules, and biological drugs such as monoclonal antibodies have difficulty in reaching intracellular targets. Macrocyclic peptides are promising candidates of PPI regulators for their potential in combining high potency and biological stability together. Cell permeability of macrocyclic peptides may also be achieved by structural modifications or conjugation to a cell-penetrating sequence. Significant progress has been made in this research area in recent years. Important technology progress and recent examples of macrocyclic peptide PPI modulators are reviewed.展开更多
Domain-based protein-protein interactions( PPIs) is a problem that has drawn the attentions of many researchers in recent years and it has been studied using lots of computational approaches from many different perspe...Domain-based protein-protein interactions( PPIs) is a problem that has drawn the attentions of many researchers in recent years and it has been studied using lots of computational approaches from many different perspectives. Existing domain-based methods to predict PPIs typically infer domain interactions from known interacting sets of proteins. However,these methods are costly and complex to implement. In this paper, a simple and effective prediction model is proposed. In this model,an improved multiinstance learning( MIL) algorithm( MilCaA) is designed that doesn't need to take the domain interactions into consideration to construct MIL bags. Then, the pseudo-amino acid composition( PseAAC) transformation method is used to encode the instances in a multi-instance bag and the principal components analysis( PCA) is also used to reduce the feature dimension. Finally, several traditional machine learning and MIL methods are used to verify the proposed model. Experimental results demonstrate that MilCaA performs better than state-of-the-art techniques including the traditional machine learning methods which are widely used in PPIs prediction.展开更多
Detailed knowledge of interfacial region between interacting proteins is not only helpful in annotating function for proteins, but also very important for structure-based drug design and disease treatment. However, th...Detailed knowledge of interfacial region between interacting proteins is not only helpful in annotating function for proteins, but also very important for structure-based drug design and disease treatment. However, this is one of the most difficult tasks and current methods are constrained by some factors. In this study, we developed a new method to predict residue-residue contacts of two interacting protein domains by integrating information about evolutionary couplings andamino acid pairwise contact potentials, as well as domain-domain interaction interfaces. The experimental results showed that our proposed method outperformed the previous method with the same datasets. Moreover, the method promises an improvement in the source of template-based protein docking.展开更多
Systems biology has become an effective approach for understanding the molecular mechanisms underlying the development of lung cancer.In this study,sequences of 100 non-small cell lung cancer (NSCLC)-related proteins ...Systems biology has become an effective approach for understanding the molecular mechanisms underlying the development of lung cancer.In this study,sequences of 100 non-small cell lung cancer (NSCLC)-related proteins were downloaded from the National Center for Biotechnology Information (NCBI) databases.The Theory of Coevolution was then used to build a protein-protein interaction (PPI) network of NSCLC.Adopting the reverse thinking approach,we analyzed the NSCLC proteins one at a time.Fifteen key proteins were identified and categorized into a special protein family F(K),which included Cyclin D1 (CCND1),E-cadherin (CDH1),Cyclin-dependent kinase inhibitor 2A (CDKN2A),chemokine (C-X-C motif) ligand 12 (CXCL12),epidermal growth factor (EGF),epidermal growth factor receptor (EGFR),TNF receptor superfamily,member 6(FAS),FK506 binding protein 12-rapamycin associated protein 1 (FRAP1),O-6-methylguanine-DNA methyltransferase (MGMT),parkinson protein 2,E3 ubiquitin protein ligase (PARK2),phosphatase and tensin homolog (PTEN),calcium channel voltage-dependent alpha 2/delta subunit 2 (CACNA2D2),tubulin beta class I (TUBB),SWI/SNF-related,matrix-associated,actin-dependent regulator of chromatin,subfamily a,member 2 (SMARCA2),and wingless-type MMTV integration site family,member 7A (WNT7A).Seven key nodes of the sub-network were identified,which included PARK2,WNT7A,SMARCA2,FRAP1,CDKN2A,CCND1,and EGFR.The PPI predictions of EGFR-EGF,PARK2-FAS,PTEN-FAS,and CACNA2D2-CDH1 were confirmed experimentally by retrieving the Biological General Repository for Interaction Datasets (BioGRID) and PubMed databases.We proposed that the 7 proteins could serve as potential diagnostic molecular markers for NSCLC.In accordance with the developmental mode of lung cancer established by Sekine et al.,we assumed that the occurrence and development of lung cancer were linked not only to gene loss in the 3p region (WNT7A,3p25) and genetic mutations in the 9p region but also to similar events in the regions of 1p36.2 (FRAP1),6q25.2-q27 (PARK2),and 11q13 (CCND1).Lastly,the invasion or metastasis of lung cancer happened.展开更多
As a multidisciplinary phenomenon,panel aeroelasticity in shock-dominated flow is featured by two primary interactions:Fluid-Structure Interactions(FSIs)and Shock-Boundary Layer Interactions(SBLIs).The former raises s...As a multidisciplinary phenomenon,panel aeroelasticity in shock-dominated flow is featured by two primary interactions:Fluid-Structure Interactions(FSIs)and Shock-Boundary Layer Interactions(SBLIs).The former raises structural concerns,and the latter is of aerodynamic interest.Thus,panel aeroelasticity in shock-dominated flow represents a vital topic for the development and optimization of supersonic vehicles and propulsion systems.This review systematically summarizes recent advances in the methodologies applied to capture structural and fluid dynamics,including theoretical models,numerical simulations,and wind tunnel experiments.The application of data-driven modal decomposition,an advanced technique to extract physically crucial features,on the topic is introduced.From the perspective of FSIs,the distinctive aeroelastic behaviors in shock-dominated flow,including hysteresis phenomena and nonlinear responses,are highlighted.From the perspective of SBLIs,the modifications in their spatial and temporal characteristics imposed by the aeroelastic responses are emphasized.Motivated by the interaction between the shock waves and structural response,different strategies have been proposed to implement aeroelastic suppression and shock control,which have the potential to enhance structural safety and aerodynamic performance in the next generation of high-speed flight vehicles.展开更多
Understanding human-virus protein-protein interactions is critical for studying molecular mechanisms driving viral infection,immune evasion,and propagation,thereby informing strategies for public health.Here,we introd...Understanding human-virus protein-protein interactions is critical for studying molecular mechanisms driving viral infection,immune evasion,and propagation,thereby informing strategies for public health.Here,we introduce a novel multimodal deep learning framework that integrates high-confidence experimental datasets to systematically predict putative interactions between human and viral proteins.Our approach incorporates two complementary tasks:binary classification for interaction prediction and conditional sequence generation to identify interacting protein partners.By leveraging protein language models and multimodal fusion,the framework demonstrates improved accuracy in identifying biologically relevant interactions.For empirical validation,we applied this method to predict severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-human interactions,identifying candidate proteins absent from training data,several of which were corroborated by independent studies.These predictions offer critical insights into potential therapeutic targets,facilitating the design of antiviral drugs and vaccines.By enabling rapid,cost-effective discovery pipelines,our study contributes to pandemic preparedness and public health interventions,underscoring its value in combating emerging infectious diseases.展开更多
Understanding the deterioration behaviors and mechanisms of rocks under thermo-hydromechanical(THM)interactions is crucial for mitigating slope instability.In this study,the physicomechanical properties of silty mudst...Understanding the deterioration behaviors and mechanisms of rocks under thermo-hydromechanical(THM)interactions is crucial for mitigating slope instability.In this study,the physicomechanical properties of silty mudstone subjected to THM interactions were investigated by triaxial tests.The underlying micro-mechanisms were revealed using microscopic tests.The triaxial test results indicate that the strength parameters of silty mudstone decrease by 89.50%(deformation modulus),78.15%(peak strength),70.58%(cohesion),and 48.65%(friction angle)under 16 THM cycles,a load of 300 kPa,and alternating between 0℃water immersion and 60℃drying.The SEM test results indicate that the deterioration of silty mudstone strength primarily results from hydrothermal-expansion softening and cracking driven by the TLHM interactions.The specimens manifest shear failure under confining pressure exceeding 140 kPa.Furthermore,a new constitutive model considering hydrothermalexpansion strain and non-linear deformation characteristics was developed.The discrepancy between the experimentally measured peak strength and the damage constitutive model prediction remains below 5%.The proposed model is verified to be in satisfactory agreement with the experimental results.The self-designed THM apparatus overcomes the limitations of traditional investigations,enabling simultaneous consideration of thermal,hydraulic,and mechanical interactions.展开更多
Recycling of waste rubber(WR)is crucial for the sustainable development of the rubber industry.The enhancement of interfacial interactions is the main strategy for waste polymer recycling.However,there is a lack of me...Recycling of waste rubber(WR)is crucial for the sustainable development of the rubber industry.The enhancement of interfacial interactions is the main strategy for waste polymer recycling.However,there is a lack of methods for enhancing the interfacial interactions for WR recycling because WR contains abundant inert C―H bonds.Herein,we designed thioctic acid inverse vulcanization copolymers to endow recycled WR with dynamic disulfide interfacial interactions,significantly improving the mechanical properties of recycled WR.These disulfide interfacial interactions among the recycled WR tend to exchange,which dramatically increases the fractocohesive length and prevents stress concentration near the crack tips.When recycled WR is subjected to external stress,the loads are redistributed across a broad region of adjacent regions instead of being concentrated on a limited length scale,which resists crack propagation.This work effectively recycled WR,providing a strategy for solvent-free reaction-derived inverse vulcanization copolymers to improve the toughness of WR recycling.展开更多
For hypersonic air-breathing vehicles,the V-shaped leading edges(VSLEs)of supersonic combustion ramjet(scramjet)inlets experience complex shock interactions and intense aerodynamic loads.This paper provides a comprehe...For hypersonic air-breathing vehicles,the V-shaped leading edges(VSLEs)of supersonic combustion ramjet(scramjet)inlets experience complex shock interactions and intense aerodynamic loads.This paper provides a comprehensive review of flow characteristics at the crotch of VSLEs,with particular focus on the transition of shock interaction types and the variation of wall heat flux under different freestream Mach numbers and geometric configurations.The mechanisms governing shock transition,unsteady oscillations,hysteresis,and three-dimensional effects in VSLE flows are first examined.Subsequently,thermal protection strategies aimed at mitigating extreme heating loads are reviewed,emphasizing their relevance to practical engineering applications.Special attention is given to recent studies addressing thermochemical nonequilibrium effects on VSLE shock interactions,and the limitations of current research are critically assessed.Finally,perspectives for future investigations into hypersonic VSLE shock interactions are outlined,highlighting opportunities for advancing design and thermal management strategies.展开更多
Luminescent metal-organic frameworks(MOFs)have garnered significant attention due to their structural tunability and potential applications in solid-state lighting,bioimaging,sensing,anticounterfeiting,and other field...Luminescent metal-organic frameworks(MOFs)have garnered significant attention due to their structural tunability and potential applications in solid-state lighting,bioimaging,sensing,anticounterfeiting,and other fields.Nevertheless,due to the tendency of1,4-benzenedicarboxylic acid(BDC)to rotate within the framework,MOFs composed of it exhibit significant non-radiative energy dissipation and thus impair the emissive properties.In this study,efficient luminescence of MIL-140A nanocrystals(NCs)with BDC rotors as ligands is achieved by pressure treatment strategy.Pressure treatment effectively modulates the pore structure of the framework,enhancing the interactions between the N,N-dimethylformamide vip molecules and the BDC ligands.The enhanced host-vip interaction contributes to the structural rigidity of the MOF,thereby suppressing the rotation-induced excited-state energy loss.As a result,the pressure-treated MIL-140A NCs displayed bright blue-light emission,with the photoluminescence quantum yield increasing from an initial 6.8%to 69.2%.This study developed an effective strategy to improve the luminescence performance of rotor ligand MOFs,offers a new avenue for the rational design and synthesis of MOFs with superior luminescent properties.展开更多
The coupled chemo-mechanical impact of supercritical CO_(2)-H_(2)O(ScCO_(2)-H_(2)O)reactions on fracture geometry and nonlinear flow regimes in deep shale under confining pressures remains inadequately quantified.This...The coupled chemo-mechanical impact of supercritical CO_(2)-H_(2)O(ScCO_(2)-H_(2)O)reactions on fracture geometry and nonlinear flow regimes in deep shale under confining pressures remains inadequately quantified.This study systematically investigates the effects of ScCO_(2)-H_(2)O-shale interactions on fracture morphology and flow properties under confining pressures from 15 MPa to 40 MPa by integrating XRD(X-ray diffraction),micro-CT,3D surface profilometry,and multistage steady-state flow experiments.The results demonstrate that ScCO_(2)-H_(2)O exposure drives pyrite/feldspar dissolution and localized clay precipitation,resulting in fracture branching and macroscopic aperture regularization.Critically,confining pressure dictates the net hydraulic response:under low confining pressure(15-25 MPa),dissolution dominates,enhancing permeability,flow efficiency(Q/VP),and pre-linear flow behavior(n<1).At high confining pressures(30-40 MPa)mechanical compaction and mineral precipitation amplify flow resistance,shifting the flow regime toward quasi-linear behavior,as inertial effects become negligible compared to dominant viscous forces and increased flow resistance.Confining pressure thus critically mediates the dissolution-precipitation balance during ScCO_(2)-H_(2)O treatment,with an optimal window of 15-25 MPa identified for enhancing conductivity while minimizing clogging risk.These findings provide a quantitative framework for predicting stress-dependent flow evolution in chemically altered shale fractures.展开更多
It has been almost 20 years since the first report of a WRKY transcription factor, SPF1, from sweet potato. Great progress has been made since then in establishing the diverse biological roles of WRKY transcription fa...It has been almost 20 years since the first report of a WRKY transcription factor, SPF1, from sweet potato. Great progress has been made since then in establishing the diverse biological roles of WRKY transcription factors in plant growth, development, and responses to biotic and abiotic stress. Despite the functional diversity, almost all ana-lyzed WRKY proteins recognize the TrGACC/T W-box sequences and, therefore, mechanisms other than mere recognition of the core W-box promoter elements are necessary to achieve the regulatory specificity of WRKY transcription factors. Research over the past several years has revealed that WRKY transcription factors physically interact with a wide range of proteins with roles in signaling, transcription, and chromatin remodeling. Studies of WRKY-interacting proteins have provided important insights into the regulation and mode of action of members of the important family of transcrip-tion factors. It has also emerged that the slightly varied WRKY domains and other protein motifs conserved within each of the seven WRKY subfamilies participate in protein-protein interactions and mediate complex functional interactions between WRKY proteins and between WRKY and other regulatory proteins in the modulation of important biologi- cal processes. In this review, we summarize studies of protein-protein interactions for WRKY transcription factors and discuss how the interacting partners contribute, at different levels, to the establishment of the complex regulatory and functional network of WRKY transcription factors.展开更多
The 90-kilo Dalton(kD) heat shock protein(Hsp90) is a ubiquitous,ATP-dependent molecular chaperone whose primary function is to ensure the proper folding of several hundred client protein substrates.Because many of th...The 90-kilo Dalton(kD) heat shock protein(Hsp90) is a ubiquitous,ATP-dependent molecular chaperone whose primary function is to ensure the proper folding of several hundred client protein substrates.Because many of these clients are overexpressed or become mutated during cancer progression,Hsp90 inhibition has been pursued as a potential strategy for cancer as one can target multiple oncoproteins and signaling pathways simultaneously.The first discovered Hsp90 inhibitors,geldanamycin and radicicol,function by competitively binding to Hsp90’s N-terminal binding site and inhibiting its ATPase activity.However,most of these N-terminal inhibitors exhibited detrimental activities during clinical evaluation due to induction of the pro-survival heat shock response as well as poor selectivity amongst the four isoforms.Consequently,alternative approaches to Hsp90 inhibition have been pursued and include C-terminal inhibition,isoform-selective inhibition,and the disruption of Hsp90 protein-protein interactions.Since the Hsp90 protein folding cycle requires the assembly of Hsp90 into a large heteroprotein complex,along with various co-chaperones and immunophilins,the development of small molecules that prevent assembly of the complex offers an alternative method of Hsp90 inhibition.展开更多
The gaseous plant hormone ethylene regulates many processes of high agronomic relevance throughout the life span of plants. A central element in ethylene signaling is the endoplasmic reticulum （ER）-Iocalized membran...The gaseous plant hormone ethylene regulates many processes of high agronomic relevance throughout the life span of plants. A central element in ethylene signaling is the endoplasmic reticulum （ER）-Iocalized membrane protein ETHYLENE INSENSITIVE2 （EIN2）. Recent studies indicate that in response to ethylene, the extra-membranous C-terminal end of EIN2 is proteolytically processed and translocated from the ER to the nucleus. Here, we report that the conserved nuclear localization signal （NLS） mediating nuclear import of the EIN2 C-terminus provides an important domain for complex formation with ethylene receptor ETHYLENE RESPONSE1 （ETR1）. EIN2 lacking the NLS domain shows strongly reduced affinity for the receptor. Interaction of EIN2 and ETR1 is also blocked by a synthetic peptide of the NLS motif. The corre- sponding peptide substantially reduces ethylene responses in planta. Our results uncover a novel mecha- nism and type of inhibitor interfering with ethylene signal transduction and ethylene responses in plants. Disruption of essential protein-protein interactions in the ethylene signaling pathway as shown in our study for the EIN2-ETR1 complex has the potential to guide the development of innovative ethylene antagonists for modern agriculture and horticulture.展开更多
Plant protein-protein interaction networks have not been identified by large-scale experiments. In order to better understand the protein interactions in rice, the Predicted Rice Interactome Network （PRIN; http：//bi...Plant protein-protein interaction networks have not been identified by large-scale experiments. In order to better understand the protein interactions in rice, the Predicted Rice Interactome Network （PRIN; http：//bis.zju.edu.cn/ prin/） presented 76,585 predicted interactions involving 5,049 rice proteins. After mapping genomic features of rice （GO annotation, subcellular localizationprediction, and gene expression）, we found that a well-annotated and biologically significant network is rich enough to capture many significant functional linkages within higher-order biological systems, such as pathways and biological processes. Furthermore, we took MADS-box do- main-containing proteins and circadian rhythm signaling pathways as examples to demonstrate that functional protein complexes and biological pathways could be effectively expanded in our predicted network. The expanded molecular network in PRIN has considerably improved the capability of these analyses to integrate existing knowledge and provide novel insights into the function and coordination of genes and gene networks.展开更多
Proteomics become an important research area of interests in life science after the completion of the human genome project.This scientific is to study the characteristics of proteins at the large-scale data level,and ...Proteomics become an important research area of interests in life science after the completion of the human genome project.This scientific is to study the characteristics of proteins at the large-scale data level,and then gain a holistic and comprehensive understanding of the process of disease occurrence and cell metabolism at the protein level.A key issue in proteomics is how to efficiently analyze the massive amounts of protein data produced by high-throughput technologies.Computational technologies with low-cost and short-cycle are becoming the preferred methods for solving some important problems in post-genome era,such as protein-protein interactions(PPIs).In this review,we focus on computational methods for PPIs detection and show recent advancements in this critical area from multiple aspects.First,we analyze in detail the several challenges for computational methods for predicting PPIs and summarize the available PPIs data sources.Second,we describe the state-of-the-art computational methods recently proposed on this topic.Finally,we discuss some important technologies that can promote the prediction of PPI and the development of computational proteomics.展开更多
Protein-protein interactions(PPls)play a crucial role in drug discovery and disease treatment.However,the development of effective drugs targeting PPls remains challenging due to limited methodologies for probing thei...Protein-protein interactions(PPls)play a crucial role in drug discovery and disease treatment.However,the development of effective drugs targeting PPls remains challenging due to limited methodologies for probing their spatiotemporal anisotropy.Here,we propose a single-molecule approach using a unique force circuit to investigate Ppl dynamics and anisotropy under mechanical forces.Unlike conventional techniques,this approach enables the manipulation and real-time monitoring of individual proteins at specific amino acids with defined geometry,offering insights into molecular mechanisms at the single-molecule level.The DNA force circuit was constructed using click chemistry conjugation methods and genetic code expansion techniques,facilitating orthogonal conjugation between proteins and nucleic acids.The SET domain of the MLL1 protein and the tail of histone H3 were used as a model system to demonstrate the application of the DNA force circuit.With the use of atomic force microscopy and magnetic tweezers,optimized assembly procedures were developed.The DNA force circuit provides an exceptional platform for studying the anisotropy of PPis and holds promise for advancing drug discovery research targeted at PPIs.展开更多
基金the National Natural Science Foundation of China(Nos.22307009,82374155,82073997,82104376)the Sichuan Science and Technology Program(Nos.2023NSFSC1108,2024NSFTD0023)+1 种基金the Postdoctoral Research Project of Sichuan Provincethe Xinglin Scholar Research Promotion Project of Chengdu University of TCM.
文摘Background:Triple-negative breast cancer(TNBC),characterized by its lack of traditional hormone receptors and HER2,presents a significant challenge in oncology due to its poor response to conventional therapies.Autophagy is an important process for maintaining cellular homeostasis,and there are currently autophagy biomarkers that play an effective role in the clinical treatment of tumors.In contrast to targeting protein activity,intervention with proteinprotein interaction(PPI)can avoid unrelated crosstalk and regulate the autophagy process with minimal interference pathways.Methods:Here,we employed Naive Bayes,Decision Tree,and k-Nearest Neighbors to elucidate the complex PPI network associated with autophagy in TNBC,aiming to uncover novel therapeutic targets.Meanwhile,the candidate proteins interacting with Beclin 2 were initially screened in MDA-MB-231 cells using Beclin 2 as bait protein by immunoprecipitation-mass spectrometry assay,and the interaction relationship was verified by molecular docking and CO-IP experiments after intersection.Colony formation,cellular immunofluorescence,cell scratch and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)tests were used to predict the clinical therapeutic effects of manipulating candidate PPI.Results:By developing three PPI classification models and analyzing over 13,000 datasets,we identified 3733 previously unknown autophagy-related PPIs.Our network analysis revealed the central role of Beclin 2 in autophagy regulation,uncovering its interactions with 39 newly identified proteins.Notably,the CO-IP studies identified the substantial interaction between Beclin 2 and Ubiquilin 1,which was anticipated by our model and discovered in immunoprecipitation-mass spectrometry assay results.Subsequently,in vitro investigations showed that overexpressing Beclin 2 increased Ubiquilin 1,promoted autophagy-dependent cell death,and inhibited proliferation and metastasis in MDA-MB-231 cells.Conclusions:This study not only enhances our understanding of autophagy regulation in TNBC but also identifies the Beclin 2-Ubiquilin 1 axis as a promising target for precision therapy.These findings open new avenues for drug discovery and offer inspiration for more effective treatments for this aggressive cancer subtype.
基金National Natural Science Foundation of China,No.31971180 and No.11474013.
文摘Almost all the cellular processes in a living system are controlled by proteins:They regulate gene expression,catalyze chemical reactions,transport small molecules across membranes,and transmit signal across membranes.Even,a viral infection is often initiated through virus-host protein interactions.Protein-protein interactions(PPIs)are the physical contacts between two or more proteins and they represent complex biological functions.Nowadays,PPIs have been used to construct PPI networks to study complex pathways for revealing the functions of unknown proteins.Scientists have used PPIs to find the molecular basis of certain diseases and also some potential drug targets.In this review,we will discuss how PPI networks are essential to understand the molecular basis of virus-host relationships and several databases which are dedicated to virus-host interaction studies.Here,we present a short but comprehensive review on PPIs,including the experimental and computational methods of finding PPIs,the databases dedicated to virus-host PPIs,and the associated various applications in protein interaction networks of some lethal viruses with their hosts.
基金supported by grants from National Natural Science Foundation of China (82090042, 31530091,81870912)National Key Research and Development Program of China (2016YFC1306703)。
文摘Neurological and neuropsychiatric disorders are one of the leading causes of disability worldwide and affect the health of billions of people.Nitric oxide(NO),a free gas with multitudinous bioactivities,is mainly produced from the oxidation of L-arginine by neuronal nitric oxide synthase(nNOS)in the brain.Inhibiting nNOS benefits a variety of neurological and neuropsychiatric disorders,including stroke,depression and anxiety disorders,posttraumatic stress disorder,Parkinson’s disease,Alzheimer’s disease,chronic pain,and drug addiction.Due to critical roles of nNOS in learning and memory and synaptic plasticity,direct inhibition of nNOS may cause severe side effects.Importantly,interactions of several proteins,including post-synaptic density 95(PSD-95),carboxyterminal PDZ ligand of nNOS(CAPON)and serotonin transporter(SERT),with the PSD/Disc-large/ZO-1 homologous(PDZ)domain of nNOS have been demonstrated to influence the subcellular distribution and activity of the enzyme in the brain.Therefore,it will be a preferable means to interfere with nNOS-mediated proteinprotein interactions(PPIs),which do not lead to undesirable effects.Herein,we summarize the current literatures on nNOS-mediated PPIs involved in neurological and neuropsychiatric disorders,and the discovery of drugs targeting the PPIs,which is expected to provide potential targets for developing novel drugs and new strategy for the treatment of neurological and neuropsychiatric disorders.
基金supported by Principle Training Program of Education Department of Sichuan Province (No. 18CZ0042)Fundamental Research Fund of Chengdu University (No. 2081916027)Undergraduate Innovation Programm of Chengdu University (Nos. CDU_CX_2018250, CDU_CX_2018251)
文摘Protein-protein interactions(PPIs) are recognized as attractive therapeutic targets. However targeting PPIs especially intracellular ones has been proven extremely difficult for conventional drug-like small molecules, and biological drugs such as monoclonal antibodies have difficulty in reaching intracellular targets. Macrocyclic peptides are promising candidates of PPI regulators for their potential in combining high potency and biological stability together. Cell permeability of macrocyclic peptides may also be achieved by structural modifications or conjugation to a cell-penetrating sequence. Significant progress has been made in this research area in recent years. Important technology progress and recent examples of macrocyclic peptide PPI modulators are reviewed.
基金National Natural Science Foundations of China(Nos.61503116,61402007)Foundation for Young Talents in the Colleges of Anhui Province Committee,China(No.2013SQRL097ZD)+1 种基金Natural Science Foundation of Anhui Educational Committee,China(No.KJ2014A198)Natural Science Foundation of Anhui Province,China(No.1408085QF108)
文摘Domain-based protein-protein interactions( PPIs) is a problem that has drawn the attentions of many researchers in recent years and it has been studied using lots of computational approaches from many different perspectives. Existing domain-based methods to predict PPIs typically infer domain interactions from known interacting sets of proteins. However,these methods are costly and complex to implement. In this paper, a simple and effective prediction model is proposed. In this model,an improved multiinstance learning( MIL) algorithm( MilCaA) is designed that doesn't need to take the domain interactions into consideration to construct MIL bags. Then, the pseudo-amino acid composition( PseAAC) transformation method is used to encode the instances in a multi-instance bag and the principal components analysis( PCA) is also used to reduce the feature dimension. Finally, several traditional machine learning and MIL methods are used to verify the proposed model. Experimental results demonstrate that MilCaA performs better than state-of-the-art techniques including the traditional machine learning methods which are widely used in PPIs prediction.
文摘Detailed knowledge of interfacial region between interacting proteins is not only helpful in annotating function for proteins, but also very important for structure-based drug design and disease treatment. However, this is one of the most difficult tasks and current methods are constrained by some factors. In this study, we developed a new method to predict residue-residue contacts of two interacting protein domains by integrating information about evolutionary couplings andamino acid pairwise contact potentials, as well as domain-domain interaction interfaces. The experimental results showed that our proposed method outperformed the previous method with the same datasets. Moreover, the method promises an improvement in the source of template-based protein docking.
基金supported by National Natural Science Foundation of China (No.91130009)Science and Technology Planning Project of Guangdong Province of China(No.2003A3080503)
文摘Systems biology has become an effective approach for understanding the molecular mechanisms underlying the development of lung cancer.In this study,sequences of 100 non-small cell lung cancer (NSCLC)-related proteins were downloaded from the National Center for Biotechnology Information (NCBI) databases.The Theory of Coevolution was then used to build a protein-protein interaction (PPI) network of NSCLC.Adopting the reverse thinking approach,we analyzed the NSCLC proteins one at a time.Fifteen key proteins were identified and categorized into a special protein family F(K),which included Cyclin D1 (CCND1),E-cadherin (CDH1),Cyclin-dependent kinase inhibitor 2A (CDKN2A),chemokine (C-X-C motif) ligand 12 (CXCL12),epidermal growth factor (EGF),epidermal growth factor receptor (EGFR),TNF receptor superfamily,member 6(FAS),FK506 binding protein 12-rapamycin associated protein 1 (FRAP1),O-6-methylguanine-DNA methyltransferase (MGMT),parkinson protein 2,E3 ubiquitin protein ligase (PARK2),phosphatase and tensin homolog (PTEN),calcium channel voltage-dependent alpha 2/delta subunit 2 (CACNA2D2),tubulin beta class I (TUBB),SWI/SNF-related,matrix-associated,actin-dependent regulator of chromatin,subfamily a,member 2 (SMARCA2),and wingless-type MMTV integration site family,member 7A (WNT7A).Seven key nodes of the sub-network were identified,which included PARK2,WNT7A,SMARCA2,FRAP1,CDKN2A,CCND1,and EGFR.The PPI predictions of EGFR-EGF,PARK2-FAS,PTEN-FAS,and CACNA2D2-CDH1 were confirmed experimentally by retrieving the Biological General Repository for Interaction Datasets (BioGRID) and PubMed databases.We proposed that the 7 proteins could serve as potential diagnostic molecular markers for NSCLC.In accordance with the developmental mode of lung cancer established by Sekine et al.,we assumed that the occurrence and development of lung cancer were linked not only to gene loss in the 3p region (WNT7A,3p25) and genetic mutations in the 9p region but also to similar events in the regions of 1p36.2 (FRAP1),6q25.2-q27 (PARK2),and 11q13 (CCND1).Lastly,the invasion or metastasis of lung cancer happened.
基金supported by the National Natural Science Foundation of China(No.12372233)the Innovation Foundation for Doctor Dissertation of Northwestern Polytechnical University,China(No.25GH01020005)the“111 Project”of China(No.B17037)。
文摘As a multidisciplinary phenomenon,panel aeroelasticity in shock-dominated flow is featured by two primary interactions:Fluid-Structure Interactions(FSIs)and Shock-Boundary Layer Interactions(SBLIs).The former raises structural concerns,and the latter is of aerodynamic interest.Thus,panel aeroelasticity in shock-dominated flow represents a vital topic for the development and optimization of supersonic vehicles and propulsion systems.This review systematically summarizes recent advances in the methodologies applied to capture structural and fluid dynamics,including theoretical models,numerical simulations,and wind tunnel experiments.The application of data-driven modal decomposition,an advanced technique to extract physically crucial features,on the topic is introduced.From the perspective of FSIs,the distinctive aeroelastic behaviors in shock-dominated flow,including hysteresis phenomena and nonlinear responses,are highlighted.From the perspective of SBLIs,the modifications in their spatial and temporal characteristics imposed by the aeroelastic responses are emphasized.Motivated by the interaction between the shock waves and structural response,different strategies have been proposed to implement aeroelastic suppression and shock control,which have the potential to enhance structural safety and aerodynamic performance in the next generation of high-speed flight vehicles.
基金supported by the Science and Technology Development Fund of Macao,SAR(Grant 0111/2023/AFJ and 0002/2024/RDP)the Startup Program and Self-Supporting Program of Guangzhou National Laboratory(No.YW-YFYJ0101 and No.SRPG22007)+2 种基金the CAS Research Fund(No.XDB38050200)the National Natural Science Foundation of China(No.12371485)the National Key R&D Program of China(No.2022YFF1202101).
文摘Understanding human-virus protein-protein interactions is critical for studying molecular mechanisms driving viral infection,immune evasion,and propagation,thereby informing strategies for public health.Here,we introduce a novel multimodal deep learning framework that integrates high-confidence experimental datasets to systematically predict putative interactions between human and viral proteins.Our approach incorporates two complementary tasks:binary classification for interaction prediction and conditional sequence generation to identify interacting protein partners.By leveraging protein language models and multimodal fusion,the framework demonstrates improved accuracy in identifying biologically relevant interactions.For empirical validation,we applied this method to predict severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-human interactions,identifying candidate proteins absent from training data,several of which were corroborated by independent studies.These predictions offer critical insights into potential therapeutic targets,facilitating the design of antiviral drugs and vaccines.By enabling rapid,cost-effective discovery pipelines,our study contributes to pandemic preparedness and public health interventions,underscoring its value in combating emerging infectious diseases.
基金supported by“the National Natural Science Foundation of China(52378440,52078067,52078066,42477143,52408458)the Key Science and Technology Program in the Transportation Industry(2022-MS1-032,2022-MS5-125)+4 种基金the Natural Science Foundation of Hunan Province(2023JJ10045)the Outstanding Innovative Youth Training Program of Changsha City(kq2305023)Scientific Research Foundation of Hunan Provincial Education Department(24B0292)Water Resources Science and Technology Project of Hunan Province(XSKJ2023059-41)the Guangxi Key Research and Development Program(AB23075184)。
文摘Understanding the deterioration behaviors and mechanisms of rocks under thermo-hydromechanical(THM)interactions is crucial for mitigating slope instability.In this study,the physicomechanical properties of silty mudstone subjected to THM interactions were investigated by triaxial tests.The underlying micro-mechanisms were revealed using microscopic tests.The triaxial test results indicate that the strength parameters of silty mudstone decrease by 89.50%(deformation modulus),78.15%(peak strength),70.58%(cohesion),and 48.65%(friction angle)under 16 THM cycles,a load of 300 kPa,and alternating between 0℃water immersion and 60℃drying.The SEM test results indicate that the deterioration of silty mudstone strength primarily results from hydrothermal-expansion softening and cracking driven by the TLHM interactions.The specimens manifest shear failure under confining pressure exceeding 140 kPa.Furthermore,a new constitutive model considering hydrothermalexpansion strain and non-linear deformation characteristics was developed.The discrepancy between the experimentally measured peak strength and the damage constitutive model prediction remains below 5%.The proposed model is verified to be in satisfactory agreement with the experimental results.The self-designed THM apparatus overcomes the limitations of traditional investigations,enabling simultaneous consideration of thermal,hydraulic,and mechanical interactions.
基金financially supported by the National Natural Science Foundation of China(No.52363007)。
文摘Recycling of waste rubber(WR)is crucial for the sustainable development of the rubber industry.The enhancement of interfacial interactions is the main strategy for waste polymer recycling.However,there is a lack of methods for enhancing the interfacial interactions for WR recycling because WR contains abundant inert C―H bonds.Herein,we designed thioctic acid inverse vulcanization copolymers to endow recycled WR with dynamic disulfide interfacial interactions,significantly improving the mechanical properties of recycled WR.These disulfide interfacial interactions among the recycled WR tend to exchange,which dramatically increases the fractocohesive length and prevents stress concentration near the crack tips.When recycled WR is subjected to external stress,the loads are redistributed across a broad region of adjacent regions instead of being concentrated on a limited length scale,which resists crack propagation.This work effectively recycled WR,providing a strategy for solvent-free reaction-derived inverse vulcanization copolymers to improve the toughness of WR recycling.
基金funded by the Research Fund of National Key Laboratory of Aerospace Physics in Fluids,grant number 2024-APF-KFZD-01Guangdong Basic and Applied Basic Research Foundation,grant number 2025A1515012081+1 种基金National Natural Science Foundation of China,grant number 12002193Shandong Provincial Natural Science Foundation,China,grant number ZR2019QA018.
文摘For hypersonic air-breathing vehicles,the V-shaped leading edges(VSLEs)of supersonic combustion ramjet(scramjet)inlets experience complex shock interactions and intense aerodynamic loads.This paper provides a comprehensive review of flow characteristics at the crotch of VSLEs,with particular focus on the transition of shock interaction types and the variation of wall heat flux under different freestream Mach numbers and geometric configurations.The mechanisms governing shock transition,unsteady oscillations,hysteresis,and three-dimensional effects in VSLE flows are first examined.Subsequently,thermal protection strategies aimed at mitigating extreme heating loads are reviewed,emphasizing their relevance to practical engineering applications.Special attention is given to recent studies addressing thermochemical nonequilibrium effects on VSLE shock interactions,and the limitations of current research are critically assessed.Finally,perspectives for future investigations into hypersonic VSLE shock interactions are outlined,highlighting opportunities for advancing design and thermal management strategies.
基金supported by the National Key R&D Program of China(Grant No.2023YFA1406200)the National Natural Science Foundation of China(No.12274177 and 12304261)the China Postdoctoral Science Foundation(No.2024M751076)。
文摘Luminescent metal-organic frameworks(MOFs)have garnered significant attention due to their structural tunability and potential applications in solid-state lighting,bioimaging,sensing,anticounterfeiting,and other fields.Nevertheless,due to the tendency of1,4-benzenedicarboxylic acid(BDC)to rotate within the framework,MOFs composed of it exhibit significant non-radiative energy dissipation and thus impair the emissive properties.In this study,efficient luminescence of MIL-140A nanocrystals(NCs)with BDC rotors as ligands is achieved by pressure treatment strategy.Pressure treatment effectively modulates the pore structure of the framework,enhancing the interactions between the N,N-dimethylformamide vip molecules and the BDC ligands.The enhanced host-vip interaction contributes to the structural rigidity of the MOF,thereby suppressing the rotation-induced excited-state energy loss.As a result,the pressure-treated MIL-140A NCs displayed bright blue-light emission,with the photoluminescence quantum yield increasing from an initial 6.8%to 69.2%.This study developed an effective strategy to improve the luminescence performance of rotor ligand MOFs,offers a new avenue for the rational design and synthesis of MOFs with superior luminescent properties.
基金support from the Science and Technology Innovation Program of Hunan Province(Grant No.2023RC1021)the Natural Science Foundation of Sichuan Province(Grant No.2025YFHZ0323).-。
文摘The coupled chemo-mechanical impact of supercritical CO_(2)-H_(2)O(ScCO_(2)-H_(2)O)reactions on fracture geometry and nonlinear flow regimes in deep shale under confining pressures remains inadequately quantified.This study systematically investigates the effects of ScCO_(2)-H_(2)O-shale interactions on fracture morphology and flow properties under confining pressures from 15 MPa to 40 MPa by integrating XRD(X-ray diffraction),micro-CT,3D surface profilometry,and multistage steady-state flow experiments.The results demonstrate that ScCO_(2)-H_(2)O exposure drives pyrite/feldspar dissolution and localized clay precipitation,resulting in fracture branching and macroscopic aperture regularization.Critically,confining pressure dictates the net hydraulic response:under low confining pressure(15-25 MPa),dissolution dominates,enhancing permeability,flow efficiency(Q/VP),and pre-linear flow behavior(n<1).At high confining pressures(30-40 MPa)mechanical compaction and mineral precipitation amplify flow resistance,shifting the flow regime toward quasi-linear behavior,as inertial effects become negligible compared to dominant viscous forces and increased flow resistance.Confining pressure thus critically mediates the dissolution-precipitation balance during ScCO_(2)-H_(2)O treatment,with an optimal window of 15-25 MPa identified for enhancing conductivity while minimizing clogging risk.These findings provide a quantitative framework for predicting stress-dependent flow evolution in chemically altered shale fractures.
文摘It has been almost 20 years since the first report of a WRKY transcription factor, SPF1, from sweet potato. Great progress has been made since then in establishing the diverse biological roles of WRKY transcription factors in plant growth, development, and responses to biotic and abiotic stress. Despite the functional diversity, almost all ana-lyzed WRKY proteins recognize the TrGACC/T W-box sequences and, therefore, mechanisms other than mere recognition of the core W-box promoter elements are necessary to achieve the regulatory specificity of WRKY transcription factors. Research over the past several years has revealed that WRKY transcription factors physically interact with a wide range of proteins with roles in signaling, transcription, and chromatin remodeling. Studies of WRKY-interacting proteins have provided important insights into the regulation and mode of action of members of the important family of transcrip-tion factors. It has also emerged that the slightly varied WRKY domains and other protein motifs conserved within each of the seven WRKY subfamilies participate in protein-protein interactions and mediate complex functional interactions between WRKY proteins and between WRKY and other regulatory proteins in the modulation of important biologi- cal processes. In this review, we summarize studies of protein-protein interactions for WRKY transcription factors and discuss how the interacting partners contribute, at different levels, to the establishment of the complex regulatory and functional network of WRKY transcription factors.
基金Financial support comes from the National Institutes of Health (CA213566, USA)。
文摘The 90-kilo Dalton(kD) heat shock protein(Hsp90) is a ubiquitous,ATP-dependent molecular chaperone whose primary function is to ensure the proper folding of several hundred client protein substrates.Because many of these clients are overexpressed or become mutated during cancer progression,Hsp90 inhibition has been pursued as a potential strategy for cancer as one can target multiple oncoproteins and signaling pathways simultaneously.The first discovered Hsp90 inhibitors,geldanamycin and radicicol,function by competitively binding to Hsp90’s N-terminal binding site and inhibiting its ATPase activity.However,most of these N-terminal inhibitors exhibited detrimental activities during clinical evaluation due to induction of the pro-survival heat shock response as well as poor selectivity amongst the four isoforms.Consequently,alternative approaches to Hsp90 inhibition have been pursued and include C-terminal inhibition,isoform-selective inhibition,and the disruption of Hsp90 protein-protein interactions.Since the Hsp90 protein folding cycle requires the assembly of Hsp90 into a large heteroprotein complex,along with various co-chaperones and immunophilins,the development of small molecules that prevent assembly of the complex offers an alternative method of Hsp90 inhibition.
文摘The gaseous plant hormone ethylene regulates many processes of high agronomic relevance throughout the life span of plants. A central element in ethylene signaling is the endoplasmic reticulum （ER）-Iocalized membrane protein ETHYLENE INSENSITIVE2 （EIN2）. Recent studies indicate that in response to ethylene, the extra-membranous C-terminal end of EIN2 is proteolytically processed and translocated from the ER to the nucleus. Here, we report that the conserved nuclear localization signal （NLS） mediating nuclear import of the EIN2 C-terminus provides an important domain for complex formation with ethylene receptor ETHYLENE RESPONSE1 （ETR1）. EIN2 lacking the NLS domain shows strongly reduced affinity for the receptor. Interaction of EIN2 and ETR1 is also blocked by a synthetic peptide of the NLS motif. The corre- sponding peptide substantially reduces ethylene responses in planta. Our results uncover a novel mecha- nism and type of inhibitor interfering with ethylene signal transduction and ethylene responses in plants. Disruption of essential protein-protein interactions in the ethylene signaling pathway as shown in our study for the EIN2-ETR1 complex has the potential to guide the development of innovative ethylene antagonists for modern agriculture and horticulture.
基金supported by the National Natural Science Foundation of China(Grant No.30771326,30971743,31050110121)the National Science and Technology Project of China(Grant No.2008AA10Z125,2008ZX08003-005,2009DFA32030)the Program for New Century Excellent Talents in University of China(Grant No.NCET-07-0740)
文摘Plant protein-protein interaction networks have not been identified by large-scale experiments. In order to better understand the protein interactions in rice, the Predicted Rice Interactome Network （PRIN; http：//bis.zju.edu.cn/ prin/） presented 76,585 predicted interactions involving 5,049 rice proteins. After mapping genomic features of rice （GO annotation, subcellular localizationprediction, and gene expression）, we found that a well-annotated and biologically significant network is rich enough to capture many significant functional linkages within higher-order biological systems, such as pathways and biological processes. Furthermore, we took MADS-box do- main-containing proteins and circadian rhythm signaling pathways as examples to demonstrate that functional protein complexes and biological pathways could be effectively expanded in our predicted network. The expanded molecular network in PRIN has considerably improved the capability of these analyses to integrate existing knowledge and provide novel insights into the function and coordination of genes and gene networks.
基金This work was supported in part by Awardee of the NSFC Excellent Young Scholars Program in 2017,in part by the National Natural Science Foundation of China(Grant Nos.61902342,61722212 and 61572506).
文摘Proteomics become an important research area of interests in life science after the completion of the human genome project.This scientific is to study the characteristics of proteins at the large-scale data level,and then gain a holistic and comprehensive understanding of the process of disease occurrence and cell metabolism at the protein level.A key issue in proteomics is how to efficiently analyze the massive amounts of protein data produced by high-throughput technologies.Computational technologies with low-cost and short-cycle are becoming the preferred methods for solving some important problems in post-genome era,such as protein-protein interactions(PPIs).In this review,we focus on computational methods for PPIs detection and show recent advancements in this critical area from multiple aspects.First,we analyze in detail the several challenges for computational methods for predicting PPIs and summarize the available PPIs data sources.Second,we describe the state-of-the-art computational methods recently proposed on this topic.Finally,we discuss some important technologies that can promote the prediction of PPI and the development of computational proteomics.
基金This work was supported by the National Natural Science Foundation of China[Grant 32071227 to Z.Y.,Grant 12275137 to Y.L.]Tianjin Municipal Natural Science Foundation of China(22JCYBJC01070 to Z.Y.)State Key Laboratory of Precision Measuring Technology and Instruments(Tianjin University)[Grant pilab2210 to Z.Y.].
文摘Protein-protein interactions(PPls)play a crucial role in drug discovery and disease treatment.However,the development of effective drugs targeting PPls remains challenging due to limited methodologies for probing their spatiotemporal anisotropy.Here,we propose a single-molecule approach using a unique force circuit to investigate Ppl dynamics and anisotropy under mechanical forces.Unlike conventional techniques,this approach enables the manipulation and real-time monitoring of individual proteins at specific amino acids with defined geometry,offering insights into molecular mechanisms at the single-molecule level.The DNA force circuit was constructed using click chemistry conjugation methods and genetic code expansion techniques,facilitating orthogonal conjugation between proteins and nucleic acids.The SET domain of the MLL1 protein and the tail of histone H3 were used as a model system to demonstrate the application of the DNA force circuit.With the use of atomic force microscopy and magnetic tweezers,optimized assembly procedures were developed.The DNA force circuit provides an exceptional platform for studying the anisotropy of PPis and holds promise for advancing drug discovery research targeted at PPIs.
