Nuclear magnetic resonance(NMR)spectroscopy is an indispensable tool to probe weak protein-ligand interactions,which are key to the hit identification and hit-to-lead evolution in fragment-based drug discovery(FBDD).T...Nuclear magnetic resonance(NMR)spectroscopy is an indispensable tool to probe weak protein-ligand interactions,which are key to the hit identification and hit-to-lead evolution in fragment-based drug discovery(FBDD).The integration of NMR technology in FBDD has facilitated the development of a diverse array of candidate compounds and FDAapproved drugs.Here,we summarized the rapid advancement and application of NMR techniques in contemporary China,which serves as a catalyst for the ongoing prosperousness of fragment-derived inhibitors against various targets.展开更多
WITHDRAWAL:Zhang,J.J.,Guo,Y.Q.,Qin,Z.Y.,Wei,C.T.,Hu,Q.H.,Vandeginste,V.,Miao,H.Y.,Yao,P.,and Zhang,P.F.,“Predicting Irreducible Water Saturation of Unconventional Reservoirs by Using NMR T2 Spectra:Methods of Morphol...WITHDRAWAL:Zhang,J.J.,Guo,Y.Q.,Qin,Z.Y.,Wei,C.T.,Hu,Q.H.,Vandeginste,V.,Miao,H.Y.,Yao,P.,and Zhang,P.F.,“Predicting Irreducible Water Saturation of Unconventional Reservoirs by Using NMR T2 Spectra:Methods of Morphological Division and Fractal Models”,Acta Geologica Sinica-English Edition(Accepted Article):https://doi.org/10.1111/1755-6724.15094.展开更多
为改进现有基于核磁共振(nuclear magnetic resonance,NMR)的饱和土渗透系数预测模型,提高NMR技术预测饱和土渗透系数的精度,在NMR弛豫时间T_(2)谱曲线及毛细管理论基础上,考虑毛细管迂曲度对渗透系数的影响,建立适用于饱和土体的渗透...为改进现有基于核磁共振(nuclear magnetic resonance,NMR)的饱和土渗透系数预测模型,提高NMR技术预测饱和土渗透系数的精度,在NMR弛豫时间T_(2)谱曲线及毛细管理论基础上,考虑毛细管迂曲度对渗透系数的影响,建立适用于饱和土体的渗透系数新模型。为验证该模型的准确性,对取自济南地铁裴家营站的粉质黏土试样进行固结渗透试验和核磁共振试验,分析固结过程中试样孔隙和渗透系数的变化规律,测定不同孔隙比状态下试样的渗透系数及T_(2)谱曲线,利用新模型对试样不同T_(2)谱曲线的饱和渗透系数进行预测,并与已有的4个核磁渗透系数模型预测结果进行比较。结果表明:本次试样的孔隙以小孔隙和中孔隙为主,固结中总孔隙的减小主要源自中孔隙的压缩;试样渗透系数随孔隙比降低而降低,两者间呈幂函数关系;在核磁T_(2)谱曲线和毛细管模型的基础上引入平均迂曲度可有效提高饱和土渗透系数预测精度,较已有模型,本研究新模型的预测值与实测值间的均方根误差降低43.1%~67.0%。展开更多
为了精确表征压实石英的孔径分布,文章联合核磁共振(Nuclear Magnetic Resonance,NMR)技术和X射线计算机断层扫描(Computed Tomography,CT)技术对3种干密度压实石英的孔径分布进行了定量分析,同时对比了两种方法表征石英孔径分布的优缺...为了精确表征压实石英的孔径分布,文章联合核磁共振(Nuclear Magnetic Resonance,NMR)技术和X射线计算机断层扫描(Computed Tomography,CT)技术对3种干密度压实石英的孔径分布进行了定量分析,同时对比了两种方法表征石英孔径分布的优缺点。结果表明:基于T_(1)和T_(2)曲线的NMR法分析石英孔径分布范围基本重合;基于T_(2)曲线的NMR法与CT法所测得的石英孔径分布范围存在差异,但总体趋势相同,NMR法测得的石英的最大孔径、平均孔径均大于CT法测得的数据。NMR法测得的孔径分布包括小孔,难以体现孔隙的复杂程度,CT法能捕捉复杂孔隙,但孔径分布缺少小孔。结合两种方法可以比较全面地分析石英的孔径分布。展开更多
Organic structure directingagents(OSDAs),suchas tetrapropylammonium(TPA)cations,serve as crucial templates for the formation of zeolite frameworks.These organic molecules interact with inorganic species,guiding the as...Organic structure directingagents(OSDAs),suchas tetrapropylammonium(TPA)cations,serve as crucial templates for the formation of zeolite frameworks.These organic molecules interact with inorganic species,guiding the assembly of the zeolite structure.In this study,we inves-tigate the complex interplay between boron species and TPA cations during the crystallization of[B,Al]-ZSM-5 zeolites.Two-dimensional(2D)11B-{1H}cross-polarization heteronuclear correlation(CP-HECTOR)NMRexperiments elucidate distinct interactions between two boron species,B(IV)-1 and B(IV)-2,and the propyl chain of the TPAs.Amorphous B(IV)-1 species exhibit a strong preference for proximity to the nitrogen cation center of the OSDAs,while framework B(IV)-2 species engage with components situated at greater distances from the cation center.Moreover,13C-{11B}symmetry-based resonance-echo saturation-pulse double-resonance(S-RESPDOR)experiments revealed that framework boron species preferentially occupy the straight channels of the MFI structure,as evidenced by their interaction with specificmethyl groups on the TPAmolecules.This observation provides valuable insights into the crystallization mechanism of boron-based zeolites,suggesting that the conformation and orientation of the OSDA molecules play a critical role in determining the location of boron atoms within the zeolite framework.展开更多
Ribonucleic acid(RNA)structures and dynamics play a crucial role in elucidating RNA functions and facilitating the design of drugs targeting RNA and RNA-protein complexes.However,obtaining RNA structures using convent...Ribonucleic acid(RNA)structures and dynamics play a crucial role in elucidating RNA functions and facilitating the design of drugs targeting RNA and RNA-protein complexes.However,obtaining RNA structures using conventional biophysical techniques,such as Xray crystallography and solution nuclear magnetic resonance(NMR),presents challenges due to the inherent flexibility and susceptibility to degradation of RNA.In recent years,solid-state NMR(SSNMR)has rapidly emerged as a promising alternative technique for characterizing RNA structure and dynamics.SSNMR has several distinct advantages,including flexibility in sample states,the ability to capture dynamic features of RNA in solid form,and suitability to character RNAs in various sizes.Recent decade witnessed the growth of ^(1)H-detected SSNMR methods on RNA,which targeted elucidating RNA topology and base pair dynamics in solid state.They have been applied to determine the topology of RNA segment in human immunodeficiency virus(HIV)genome and the base pair dynamics of riboswitch RNA.These advancements have expanded the utility of SSNMR techniques within the RNA research field.This review provides a comprehensive discussion of recent progress in ^(1)H-detected SSNMR investigations into RNA structure and dynamics.We focus on the established ^(1)H-detected SSNMR methods,sample preparation protocols,and the implementation of rapid data acquisition approaches.展开更多
Rat sarcoma virus oncogene(RAS)proteins are of crucial oncogenic proteins and are involved in several essential intracellular processes.The RAS protein has an intrinsic metal binding site for Mg^(2+),which is importan...Rat sarcoma virus oncogene(RAS)proteins are of crucial oncogenic proteins and are involved in several essential intracellular processes.The RAS protein has an intrinsic metal binding site for Mg^(2+),which is important for the conformational stability of the active site.Recently,it was reported that a second metal ion binding site,located further from the active site in HRAS(Harvey RAS homolog),binds Ca^(2+) with millimolar affinity.As one of the most abundant metal ions in cells,Mn^(2+) is a potential candidate for the second metal ion binding site in RAS proteins.Here,we examined the interaction of Mn^(2+) with HRAS and KRAS(Kirsten RAS homolog)using high resolution NMR spectroscopy.The NMR data showed that both the second metal ion binding site and the switch I and II regions bind Mn^(2+) in the RAS proteins.Furthermore,our paramagnetic NMR results disclosed the conformational differences in helix a3 and the following loop between HRAS and KRAS,accompanied by the association with metal ion binding.These results provide new insights into the interaction of RAS proteins and Mn^(2+) in the respective biological processes in cells.展开更多
HCLS1-associated protein X-1(HAX1)is a multifunctional mitochondrial protein involved in the regulation of apoptosis,a crucial process of programmed cell death,and mRNA processing.Despite its significance,limited stru...HCLS1-associated protein X-1(HAX1)is a multifunctional mitochondrial protein involved in the regulation of apoptosis,a crucial process of programmed cell death,and mRNA processing.Despite its significance,limited structural data is available for HAX1,hindering a comprehensive understanding of its biological function.Notably,the caseinolytic mitochondrial matrix peptidase chaperone subunit B(CLPB)has been identified as an interacting partner of HAX1,yet the biophysical properties and binding affinity governing their interaction remain poorly defined.In this study,we present a thorough biophysical characterization of full-length human HAX1 and CLPB,accomplished through recombinant expression and purification.By employing size exclusion chromatography,dynamic light scattering,and circular dichroism spectroscopy,we successfully established their biophysical properties,revealing contrasting structural features,with CLPB displaying a-helical content and HAX1 exhibiting a disordered nature.Moreover,we employed solutionstate nuclear magnetic resonance(NMR)spectroscopy to probe their binding affinity.Our findings demonstrate the formation of stable multimeric complexes between HAX1 and CLPB,and we quantified a dissociation constant in the low range of micro-molar for their high affinity interaction.These results lay the foundation for further in-depth investigations into the dynamics and energetics governing the HAX1-CLPB interaction,ultimately contributing to a comprehensive understanding of their functional mechanisms.展开更多
基金the National Key R&D Program of China(2024YFA1306200)National Natural Science Foundation of China(22377119)+2 种基金Anhui Provincial Natural Science Foundation(2208085MC50)USTC Research Funds of the Double First-Class Initiative(YD9100002028,YD9100002036)Research Funds of Center for Advanced Interdisciplinary Science and Biomedicine of IHM(QYPY20220008)for their financial support.
文摘Nuclear magnetic resonance(NMR)spectroscopy is an indispensable tool to probe weak protein-ligand interactions,which are key to the hit identification and hit-to-lead evolution in fragment-based drug discovery(FBDD).The integration of NMR technology in FBDD has facilitated the development of a diverse array of candidate compounds and FDAapproved drugs.Here,we summarized the rapid advancement and application of NMR techniques in contemporary China,which serves as a catalyst for the ongoing prosperousness of fragment-derived inhibitors against various targets.
文摘WITHDRAWAL:Zhang,J.J.,Guo,Y.Q.,Qin,Z.Y.,Wei,C.T.,Hu,Q.H.,Vandeginste,V.,Miao,H.Y.,Yao,P.,and Zhang,P.F.,“Predicting Irreducible Water Saturation of Unconventional Reservoirs by Using NMR T2 Spectra:Methods of Morphological Division and Fractal Models”,Acta Geologica Sinica-English Edition(Accepted Article):https://doi.org/10.1111/1755-6724.15094.
文摘为改进现有基于核磁共振(nuclear magnetic resonance,NMR)的饱和土渗透系数预测模型,提高NMR技术预测饱和土渗透系数的精度,在NMR弛豫时间T_(2)谱曲线及毛细管理论基础上,考虑毛细管迂曲度对渗透系数的影响,建立适用于饱和土体的渗透系数新模型。为验证该模型的准确性,对取自济南地铁裴家营站的粉质黏土试样进行固结渗透试验和核磁共振试验,分析固结过程中试样孔隙和渗透系数的变化规律,测定不同孔隙比状态下试样的渗透系数及T_(2)谱曲线,利用新模型对试样不同T_(2)谱曲线的饱和渗透系数进行预测,并与已有的4个核磁渗透系数模型预测结果进行比较。结果表明:本次试样的孔隙以小孔隙和中孔隙为主,固结中总孔隙的减小主要源自中孔隙的压缩;试样渗透系数随孔隙比降低而降低,两者间呈幂函数关系;在核磁T_(2)谱曲线和毛细管模型的基础上引入平均迂曲度可有效提高饱和土渗透系数预测精度,较已有模型,本研究新模型的预测值与实测值间的均方根误差降低43.1%~67.0%。
文摘为了精确表征压实石英的孔径分布,文章联合核磁共振(Nuclear Magnetic Resonance,NMR)技术和X射线计算机断层扫描(Computed Tomography,CT)技术对3种干密度压实石英的孔径分布进行了定量分析,同时对比了两种方法表征石英孔径分布的优缺点。结果表明:基于T_(1)和T_(2)曲线的NMR法分析石英孔径分布范围基本重合;基于T_(2)曲线的NMR法与CT法所测得的石英孔径分布范围存在差异,但总体趋势相同,NMR法测得的石英的最大孔径、平均孔径均大于CT法测得的数据。NMR法测得的孔径分布包括小孔,难以体现孔隙的复杂程度,CT法能捕捉复杂孔隙,但孔径分布缺少小孔。结合两种方法可以比较全面地分析石英的孔径分布。
基金supported by the National Energy R&D Center of Petroleum Refining Technology(RIPP,SINOPEC),the National Natural Science Foundation of China(Grants 22161132028,22172177,22225205,22372191 and 22372178)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB0540000)+2 种基金the International Partnership Program of the Chinese Academy of Sciences(314GJH2022022FN)Natural Science Foundation of Hubei Province(2021CFA021)Hubei International Scientific and Technological Cooperation Program(2024EHA043)and Base(SH2303).
文摘Organic structure directingagents(OSDAs),suchas tetrapropylammonium(TPA)cations,serve as crucial templates for the formation of zeolite frameworks.These organic molecules interact with inorganic species,guiding the assembly of the zeolite structure.In this study,we inves-tigate the complex interplay between boron species and TPA cations during the crystallization of[B,Al]-ZSM-5 zeolites.Two-dimensional(2D)11B-{1H}cross-polarization heteronuclear correlation(CP-HECTOR)NMRexperiments elucidate distinct interactions between two boron species,B(IV)-1 and B(IV)-2,and the propyl chain of the TPAs.Amorphous B(IV)-1 species exhibit a strong preference for proximity to the nitrogen cation center of the OSDAs,while framework B(IV)-2 species engage with components situated at greater distances from the cation center.Moreover,13C-{11B}symmetry-based resonance-echo saturation-pulse double-resonance(S-RESPDOR)experiments revealed that framework boron species preferentially occupy the straight channels of the MFI structure,as evidenced by their interaction with specificmethyl groups on the TPAmolecules.This observation provides valuable insights into the crystallization mechanism of boron-based zeolites,suggesting that the conformation and orientation of the OSDA molecules play a critical role in determining the location of boron atoms within the zeolite framework.
基金supported by the National Natural Science Foundation of China(grant number:22274050)the Shanghai Science and Technology Commission(contract number:23J21900300)the Fundamental Research Funds for the Central Universities.
文摘Ribonucleic acid(RNA)structures and dynamics play a crucial role in elucidating RNA functions and facilitating the design of drugs targeting RNA and RNA-protein complexes.However,obtaining RNA structures using conventional biophysical techniques,such as Xray crystallography and solution nuclear magnetic resonance(NMR),presents challenges due to the inherent flexibility and susceptibility to degradation of RNA.In recent years,solid-state NMR(SSNMR)has rapidly emerged as a promising alternative technique for characterizing RNA structure and dynamics.SSNMR has several distinct advantages,including flexibility in sample states,the ability to capture dynamic features of RNA in solid form,and suitability to character RNAs in various sizes.Recent decade witnessed the growth of ^(1)H-detected SSNMR methods on RNA,which targeted elucidating RNA topology and base pair dynamics in solid state.They have been applied to determine the topology of RNA segment in human immunodeficiency virus(HIV)genome and the base pair dynamics of riboswitch RNA.These advancements have expanded the utility of SSNMR techniques within the RNA research field.This review provides a comprehensive discussion of recent progress in ^(1)H-detected SSNMR investigations into RNA structure and dynamics.We focus on the established ^(1)H-detected SSNMR methods,sample preparation protocols,and the implementation of rapid data acquisition approaches.
基金supported by the Ministry of Science and Technology of China(2021YFA1600304)the National Natural Science Foundation of China(22161142018,21991081,22174074 and 22374126).
文摘Rat sarcoma virus oncogene(RAS)proteins are of crucial oncogenic proteins and are involved in several essential intracellular processes.The RAS protein has an intrinsic metal binding site for Mg^(2+),which is important for the conformational stability of the active site.Recently,it was reported that a second metal ion binding site,located further from the active site in HRAS(Harvey RAS homolog),binds Ca^(2+) with millimolar affinity.As one of the most abundant metal ions in cells,Mn^(2+) is a potential candidate for the second metal ion binding site in RAS proteins.Here,we examined the interaction of Mn^(2+) with HRAS and KRAS(Kirsten RAS homolog)using high resolution NMR spectroscopy.The NMR data showed that both the second metal ion binding site and the switch I and II regions bind Mn^(2+) in the RAS proteins.Furthermore,our paramagnetic NMR results disclosed the conformational differences in helix a3 and the following loop between HRAS and KRAS,accompanied by the association with metal ion binding.These results provide new insights into the interaction of RAS proteins and Mn^(2+) in the respective biological processes in cells.
基金supported by grants from the Special Foundation of President of the Chinese Academy of Sciences(Grant No.,YZJJ2020QN27,YZJJ2021QN33)Anhui Provincial Natural Science Foundation(Grant No.,2108085MC79).
文摘HCLS1-associated protein X-1(HAX1)is a multifunctional mitochondrial protein involved in the regulation of apoptosis,a crucial process of programmed cell death,and mRNA processing.Despite its significance,limited structural data is available for HAX1,hindering a comprehensive understanding of its biological function.Notably,the caseinolytic mitochondrial matrix peptidase chaperone subunit B(CLPB)has been identified as an interacting partner of HAX1,yet the biophysical properties and binding affinity governing their interaction remain poorly defined.In this study,we present a thorough biophysical characterization of full-length human HAX1 and CLPB,accomplished through recombinant expression and purification.By employing size exclusion chromatography,dynamic light scattering,and circular dichroism spectroscopy,we successfully established their biophysical properties,revealing contrasting structural features,with CLPB displaying a-helical content and HAX1 exhibiting a disordered nature.Moreover,we employed solutionstate nuclear magnetic resonance(NMR)spectroscopy to probe their binding affinity.Our findings demonstrate the formation of stable multimeric complexes between HAX1 and CLPB,and we quantified a dissociation constant in the low range of micro-molar for their high affinity interaction.These results lay the foundation for further in-depth investigations into the dynamics and energetics governing the HAX1-CLPB interaction,ultimately contributing to a comprehensive understanding of their functional mechanisms.
