Nuclear magnetic resonance(NMR)spectroscopy is a powerful and broadly used spectroscopic technique for characterizing molecular structures and dynamics.Yet the power of NMR is restricted by its inherently low sensitiv...Nuclear magnetic resonance(NMR)spectroscopy is a powerful and broadly used spectroscopic technique for characterizing molecular structures and dynamics.Yet the power of NMR is restricted by its inherently low sensitivity due to the weak polarization of nuclear spins under conventional experiment conditions.Dynamic nuclear polarization(DNP)and chemically induced dynamic nuclear polarization(CIDNP)have been emerging as powerful in-situ hyperpolarization methods to boost NMR sensitivity.This review provides a brief overview of DNP mechanisms in the context of both solid-state and liquidstate.We delve into the molecular features of different polarizing agents and their impacts on DNP applications,which are now steadily progressing towards modern NMR magnetic field strengths and ambient temperatures.Furthermore,the progress of CIDNP,particularly photo-CIDNP as a potential alternative hyperpolarization technique of DNP,in studying protein dynamics and chemical reaction mechanisms,will be covered.This review also highlights the chemical diversity and experimental strategies crucial for these hyperpolarization techniques,showcasing their transformative role in NMR spectroscopy.展开更多
All-atom molecular simulations and two-dimensional nuclear overhauser effect spectrum have been used to study the conformations of carnosine in aqueous solution. Intramolecular distances, root-mean-square deviation, r...All-atom molecular simulations and two-dimensional nuclear overhauser effect spectrum have been used to study the conformations of carnosine in aqueous solution. Intramolecular distances, root-mean-square deviation, radius of gyration, and solvent-accessible surface are used to characterize the properties of the carnosine. Carnosine can shift between extended and folded states, but exists mostly in extended state in water. Its preference for extension in pure water has been proven by the 2D nuclear magnetic resonance （NMR） experiment. The NMR experimental results are consistent with the molecular dynamics simulations.展开更多
C NMR spin-lattice relaxation times (T1), line widths, nuclear Overhauser effects (NOE) at room temperature have been measured for radiated ets 1,4-polybutadiene.With the increase of radiation dose T1 is almost invari...C NMR spin-lattice relaxation times (T1), line widths, nuclear Overhauser effects (NOE) at room temperature have been measured for radiated ets 1,4-polybutadiene.With the increase of radiation dose T1 is almost invariant, but line width of the methylene (-CH2-) carbon increases remarkably, and its NOE factor decreases sharply. This implies that the long-range segmental motion is hindered, and saturated tertiary carbon (-C H- ) is formed during crosslinking of ets 1,4-polybutadiene.展开更多
Dynamic nuclear polarization （DNP） has become a very important hyperpolarization method because it can dramatically increase the sensitivity of nuclear magnetic resonance （NMR） of various molecules. Liquid-state D...Dynamic nuclear polarization （DNP） has become a very important hyperpolarization method because it can dramatically increase the sensitivity of nuclear magnetic resonance （NMR） of various molecules. Liquid-state DNP based on Overhauser effect is capable of directly enhancing polarization of all kinds of nuclei in the system. The combination of simultaneous Overhauser multi-nuclei enhancements with the multi-nuclei parallel acquisitions provides a variety of important applications in both MR spectroscopy （MRS） and image （MRI）. Here we present two simple illustrative examples for simultaneously enhanced multi-nuclear spectra and images to demonstrate the principle and superiority. We have observed very large simultaneous DNP enhancements for different nuclei, such as XH and 23Na, 1H and 31p, 19F and 31p, especially for the first time to report sodium ion enhancement in liquid. We have also obtained the simultaneous images of 19H and 31p, 19F and 31p at low field by solution-state DNP for the first time.展开更多
The three-dimensional structure of a biomolecule rather than its one-dimensionM sequence determines its biological function. At present, the most accurate structures are derived from experimental data measured mainly ...The three-dimensional structure of a biomolecule rather than its one-dimensionM sequence determines its biological function. At present, the most accurate structures are derived from experimental data measured mainly by two techniques： X-ray crystallog- raphy and nuclear magnetic resonance （NMR） spec- troscopy. Because neither X-ray crystallography nor NMR spectroscopy could directly measure the positions of atoms in a biomolecule, algorithms must be designed to compute atom coordinates from the data. One salient feature of most NMR structure computation algorithms is their reliance on stochastic search to find the lowest energy conformations that satisfy the experimentally- derived geometric restraints. However, neither the cor- rectness of the stochastic search has been established nor the errors in the output structures could be quantified. Though there exist exact algorithms to compute struc- tures from angular restraints, similar algorithms that use distance restraints remain to be developed. An important application of structures is rational drug design where protein-ligand docking plays a crit- ical role. In fact, various docking programs that place a compound into the binding site of a target protein have been used routinely by medicinal chemists for both lead identification and optimization. Unfortunately, de- spite ongoing methodological advances and some success stories, the performance of current docking algorithms is still data-dependent. These algorithms formulate the docking problem as a match of two sets of feature points. Both the selection of feature points and the search for the best poses with the minimum scores are accomplished through some stochastic search methods. Both the un- certainty in the scoring function and the limited sam- pling space attained by the stochastic search contribute to their failures. Recently, we have developed two novel docking algorithms： a data-driven docking algorithm and a general docking algorithm that does not rely on experimental data. Our algorithms search the pose space exhaustively with the pose space itself being limited to a set of hierarchical manifolds that represent, respectively, surfaces, curves and points with unique geometric and energetic properties. These algorithms promise to be es- pecially valuable for the docking of fragments and small compounds as well as for virtual screening.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.22403029)the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(Grant No.GZC20240475,2024M760922)+5 种基金supported by National Natural Science Foundation of China(Grant No.22174099)supported by the National Natural Science Foundation of China(Grant No.22273023)the National Key R&D Program of China(Grant No.2019YFA0905200)Shanghai Municipal Natural Science Foundation(Grant No.23ZR1418200)Natural Science Foundation of Chongqing,China(Grant No.CSTB2023NSCQ-MSX0616)Shanghai Frontiers Science Center of Molecule Intelligent Syntheses,and the Fundamental Research Funds for the Central Universities.
文摘Nuclear magnetic resonance(NMR)spectroscopy is a powerful and broadly used spectroscopic technique for characterizing molecular structures and dynamics.Yet the power of NMR is restricted by its inherently low sensitivity due to the weak polarization of nuclear spins under conventional experiment conditions.Dynamic nuclear polarization(DNP)and chemically induced dynamic nuclear polarization(CIDNP)have been emerging as powerful in-situ hyperpolarization methods to boost NMR sensitivity.This review provides a brief overview of DNP mechanisms in the context of both solid-state and liquidstate.We delve into the molecular features of different polarizing agents and their impacts on DNP applications,which are now steadily progressing towards modern NMR magnetic field strengths and ambient temperatures.Furthermore,the progress of CIDNP,particularly photo-CIDNP as a potential alternative hyperpolarization technique of DNP,in studying protein dynamics and chemical reaction mechanisms,will be covered.This review also highlights the chemical diversity and experimental strategies crucial for these hyperpolarization techniques,showcasing their transformative role in NMR spectroscopy.
文摘All-atom molecular simulations and two-dimensional nuclear overhauser effect spectrum have been used to study the conformations of carnosine in aqueous solution. Intramolecular distances, root-mean-square deviation, radius of gyration, and solvent-accessible surface are used to characterize the properties of the carnosine. Carnosine can shift between extended and folded states, but exists mostly in extended state in water. Its preference for extension in pure water has been proven by the 2D nuclear magnetic resonance （NMR） experiment. The NMR experimental results are consistent with the molecular dynamics simulations.
文摘C NMR spin-lattice relaxation times (T1), line widths, nuclear Overhauser effects (NOE) at room temperature have been measured for radiated ets 1,4-polybutadiene.With the increase of radiation dose T1 is almost invariant, but line width of the methylene (-CH2-) carbon increases remarkably, and its NOE factor decreases sharply. This implies that the long-range segmental motion is hindered, and saturated tertiary carbon (-C H- ) is formed during crosslinking of ets 1,4-polybutadiene.
基金supported by the Chinese Academy of Sciences(ZDYZ2010-2)the Ministry of Science and Technology of China (2011YQ120035)the National Natural Science Foundation of China (11405264,11274347,21221064,11575287)
文摘Dynamic nuclear polarization （DNP） has become a very important hyperpolarization method because it can dramatically increase the sensitivity of nuclear magnetic resonance （NMR） of various molecules. Liquid-state DNP based on Overhauser effect is capable of directly enhancing polarization of all kinds of nuclei in the system. The combination of simultaneous Overhauser multi-nuclei enhancements with the multi-nuclei parallel acquisitions provides a variety of important applications in both MR spectroscopy （MRS） and image （MRI）. Here we present two simple illustrative examples for simultaneously enhanced multi-nuclear spectra and images to demonstrate the principle and superiority. We have observed very large simultaneous DNP enhancements for different nuclei, such as XH and 23Na, 1H and 31p, 19F and 31p, especially for the first time to report sodium ion enhancement in liquid. We have also obtained the simultaneous images of 19H and 31p, 19F and 31p at low field by solution-state DNP for the first time.
文摘The three-dimensional structure of a biomolecule rather than its one-dimensionM sequence determines its biological function. At present, the most accurate structures are derived from experimental data measured mainly by two techniques： X-ray crystallog- raphy and nuclear magnetic resonance （NMR） spec- troscopy. Because neither X-ray crystallography nor NMR spectroscopy could directly measure the positions of atoms in a biomolecule, algorithms must be designed to compute atom coordinates from the data. One salient feature of most NMR structure computation algorithms is their reliance on stochastic search to find the lowest energy conformations that satisfy the experimentally- derived geometric restraints. However, neither the cor- rectness of the stochastic search has been established nor the errors in the output structures could be quantified. Though there exist exact algorithms to compute struc- tures from angular restraints, similar algorithms that use distance restraints remain to be developed. An important application of structures is rational drug design where protein-ligand docking plays a crit- ical role. In fact, various docking programs that place a compound into the binding site of a target protein have been used routinely by medicinal chemists for both lead identification and optimization. Unfortunately, de- spite ongoing methodological advances and some success stories, the performance of current docking algorithms is still data-dependent. These algorithms formulate the docking problem as a match of two sets of feature points. Both the selection of feature points and the search for the best poses with the minimum scores are accomplished through some stochastic search methods. Both the un- certainty in the scoring function and the limited sam- pling space attained by the stochastic search contribute to their failures. Recently, we have developed two novel docking algorithms： a data-driven docking algorithm and a general docking algorithm that does not rely on experimental data. Our algorithms search the pose space exhaustively with the pose space itself being limited to a set of hierarchical manifolds that represent, respectively, surfaces, curves and points with unique geometric and energetic properties. These algorithms promise to be es- pecially valuable for the docking of fragments and small compounds as well as for virtual screening.
