Structural comparison of a new compound [（bpp）3H6]Fe2ⅢFe2ⅡMo24Ⅴ（H2PO4）8（HPO4）4（PO4）4O48（OH）12·（H2O）4·2H2O（1）[bpp=1,3-di（4-pyridyl）propane] with our previously reported two compounds [（bpy...Structural comparison of a new compound [（bpp）3H6]Fe2ⅢFe2ⅡMo24Ⅴ（H2PO4）8（HPO4）4（PO4）4O48（OH）12·（H2O）4·2H2O（1）[bpp=1,3-di（4-pyridyl）propane] with our previously reported two compounds [（bpy）3FeⅡ]3·Fe2ⅢFe2ⅡMo24Ⅴ（H2PO4）8（HPO4）4（PO4）4O48（OH）12（H2O）4·12H2O（2） and [（bpy）3FeⅡ]2FeⅡFeⅢMo12Ⅴ（H2PO4）2（H2-xPO4）.（H1＋xPO4）（HPO4）2（PO4）2O24（OH）6（H2O）2·9H2O（x=0-1）（3）（bpy=2,2＇-bipyridine）,which all exhibit one-dimensional mixed-valence iron molybdophosphate anionic chains constructed by alternating connection of FeⅢ ions and magic [FeⅡ（Mo6P4O31）2] units,reveals that the non-hydrogen atomic ratios of Mo∶Fe∶P∶O within the polymeric anionic chains are the same for all the three compounds,while the polymeric anionic chains of the different compounds bear different numbers of negative charges.And therefore there exist different numbers of counter cations per {Fe2Ⅲ[Fe2Ⅱ（P16Mo24ⅤO124）]} unit found in the titled compounds.It discloses that not only are the spatial assembling of counter cations and polymeric inorganic chains of three compounds quite different,but also the O-FeⅢ-O bond angles and FeⅢ-O bond lengths of the three different inorganic chains exhibit small differences.What is more important is that such small changes in bond length and bond angle in the assemblage of FeⅢ-O bonds lead to the considerable fluctuations of inorganic chains in their structural conformation within the three compounds,reflecting an interesting phenomenon of＂flexibility＂ in the pure inorganic one dimensional mixed-valence iron molybdophosphate chains.展开更多
In this paper, two molecular mathematical models which simulate the conformations of a random flight chain and a freely rotating chain were suggested separately from the theory of stochastic process. We had obtained a...In this paper, two molecular mathematical models which simulate the conformations of a random flight chain and a freely rotating chain were suggested separately from the theory of stochastic process. We had obtained a series of results relating to conformations by means of these models. These results are not only mathematically stricter but also include the results obtained by previous workers. In an ideal state, conformation of a random flight chain is simulated as a 3-dimensional Brownian motion {r_t(ω), t>0}. We pointed out the objective meaning which was endowed to the different variables involved in a 3-dimensional Brownian motion. On this basis, the bond vector and the end-to-end state vector were defined; the distribution function and the reduced functions were thus obtained, e.g. the distribution of the end-to-end state vector which is a measure of the flexibility of a polymer chain,展开更多
The crystallographic temperature factors （B factor） of individual atoms contain important information about the thermal motion of the atoms in a macromolecule. Previously the theory of flexibility of active site has...The crystallographic temperature factors （B factor） of individual atoms contain important information about the thermal motion of the atoms in a macromolecule. Previously the theory of flexibility of active site has been established based on the observation that the enzyme activity is sensitive to low concentration denaturing agents. It has been found that the loss of enzyme activity occurs well before the disruption of the three-dimensional structural scaffold of the enzyme. To test the theory of conformational flexibility of enzyme active site, crystal structures were perturbed by soaking in low concentration guanidine hydrochloride solutions. It was found that many lysozyme crystals tested could still diffract until the concentration of guanidine hydrochloride reached 3 M. It was also found that the B factors averaged over individually collected data sets were more accurate. Thus it suggested that accurate measurement of crystal temperature factors could be achieved for medium-high or even medium resolution crystals by averaging over multiple data sets. Furthermore, we found that the correctly predicted active sites included not only the more flexible residues, but also some more rigid residues. Both the flexible and the rigid residues in the active site played an important role in forming the active site residue network, covering the majority of the substrate binding residues. Therefore, this experimental prediction method may be useful for characterizing the binding site and the function of a protein, such as drug targeting.展开更多
Proteins are crucial to most biological processes, such as enzymes, and in various catalytic processes a dynamic motion is required. The dynamics of protein are embodied as a conformational change, which is closely re...Proteins are crucial to most biological processes, such as enzymes, and in various catalytic processes a dynamic motion is required. The dynamics of protein are embodied as a conformational change, which is closely related to the flexibility of protein. Recently, nanopore sensors have become accepted as a low cost and high throughput method to study the features of proteins. In this article, we used a SiN nanopore device to study the flexibility of T7 RNA polymerase（RNAP） and its complex with DNA promoter. By calculating full-width at half-maximum（FWHM） of Gaussian fits to the blockade histograms, we found that T7 RNAP becomes more flexible after binding DNA promoter. Moreover, the distribution of fractional current blockade suggests that flexibility alters due to a breath-like change of the volume.展开更多
Understanding the conformational flexibility of the insulin drugs is of great importance for the treatment of diabetes mellitus. Once in the body, the drug must have a certain degree of mobility within a specified per...Understanding the conformational flexibility of the insulin drugs is of great importance for the treatment of diabetes mellitus. Once in the body, the drug must have a certain degree of mobility within a specified period of time for the manifestation of its pharmacological properties. This mobility ensures conformational states necessary for binding with the insulin receptor and activating specific biological processes. In this work we investigated conformational flexibility of the pharmacologically important insulin analogues—insulin lispro, insulin aspart, insulin glulisine, and insulin glargine, using the molecular dynamics simulation method. This study provides new insight into the nature of behaviour of A-and B-chains. It has been found out that B-chain substitutions result in rapid acting, while long-lasting action can be achieved by substitutions in both chains. The results of this study can be used for development of new insulin-based antidiabetic drugs.展开更多
基金Supported by the National Natural Science Foundation of China（Nos.20771012, 20541001）.
文摘Structural comparison of a new compound [（bpp）3H6]Fe2ⅢFe2ⅡMo24Ⅴ（H2PO4）8（HPO4）4（PO4）4O48（OH）12·（H2O）4·2H2O（1）[bpp=1,3-di（4-pyridyl）propane] with our previously reported two compounds [（bpy）3FeⅡ]3·Fe2ⅢFe2ⅡMo24Ⅴ（H2PO4）8（HPO4）4（PO4）4O48（OH）12（H2O）4·12H2O（2） and [（bpy）3FeⅡ]2FeⅡFeⅢMo12Ⅴ（H2PO4）2（H2-xPO4）.（H1＋xPO4）（HPO4）2（PO4）2O24（OH）6（H2O）2·9H2O（x=0-1）（3）（bpy=2,2＇-bipyridine）,which all exhibit one-dimensional mixed-valence iron molybdophosphate anionic chains constructed by alternating connection of FeⅢ ions and magic [FeⅡ（Mo6P4O31）2] units,reveals that the non-hydrogen atomic ratios of Mo∶Fe∶P∶O within the polymeric anionic chains are the same for all the three compounds,while the polymeric anionic chains of the different compounds bear different numbers of negative charges.And therefore there exist different numbers of counter cations per {Fe2Ⅲ[Fe2Ⅱ（P16Mo24ⅤO124）]} unit found in the titled compounds.It discloses that not only are the spatial assembling of counter cations and polymeric inorganic chains of three compounds quite different,but also the O-FeⅢ-O bond angles and FeⅢ-O bond lengths of the three different inorganic chains exhibit small differences.What is more important is that such small changes in bond length and bond angle in the assemblage of FeⅢ-O bonds lead to the considerable fluctuations of inorganic chains in their structural conformation within the three compounds,reflecting an interesting phenomenon of＂flexibility＂ in the pure inorganic one dimensional mixed-valence iron molybdophosphate chains.
文摘In this paper, two molecular mathematical models which simulate the conformations of a random flight chain and a freely rotating chain were suggested separately from the theory of stochastic process. We had obtained a series of results relating to conformations by means of these models. These results are not only mathematically stricter but also include the results obtained by previous workers. In an ideal state, conformation of a random flight chain is simulated as a 3-dimensional Brownian motion {r_t(ω), t>0}. We pointed out the objective meaning which was endowed to the different variables involved in a 3-dimensional Brownian motion. On this basis, the bond vector and the end-to-end state vector were defined; the distribution function and the reduced functions were thus obtained, e.g. the distribution of the end-to-end state vector which is a measure of the flexibility of a polymer chain,
文摘为寻找新型乙酰羟酸合成酶(EC2.2.1.6,AHAS)抑制剂以克服由靶标突变(P197L突变)所引起的杂草抗性问题,利用"构象柔性度分析"策略设计、合成了一系列烷氧基取代的嘧啶水杨酸衍生物.其中, 9个化合物对P197L突变型AHAS的抗性倍数(RF值)均小于等于1,在酶水平上具有良好的反抗性.特别是2-((4,6-二甲氧基嘧啶-2-基)氧基)-6-(2-氟乙氧基)苯甲酸(5l),被进一步确定为该系列最有效的反抗性AHAS抑制剂(RF=0.31),不仅与氯磺隆(RF=2060)和双草醚(RF=4.57)相比抗性程度大幅降低,并且对野生型At AHAS和P197L突变体的抑制活性均达到了亚微摩尔水平,优于双草醚.此外,在150gai/ha的施用剂量下,2-((4,6-二甲氧基嘧啶-2-基)氧基)-6-(2-(甲氧基)乙氧基)苯甲酸(5a)、2-((4,6-二甲氧基嘧啶-2-基)氧基)-6-(3-(甲氧基)丙氧基)苯甲酸(5f)、2-((4,6-二甲氧基嘧啶-2-基)氧基)-6-(2-氟乙氧基)苯甲酸(5l)和2-((4,6-二甲氧基嘧啶-2-基)氧基)-6-(2,2-二氟乙氧基)苯甲酸(5m)对敏感型和抗性(P197L-AHAS)播娘蒿同时表现出优异的除草活性.值得注意的是,即使在最低剂量37.5 g ai/ha下,化合物5l对这两种杂草的除草防效仍超过85%,表现出良好的活体反抗性,具有深入研究的价值.
基金Project supported by the National Natural Science Foundation of China (Grant Nos. 10674172 and 10874229)
文摘The crystallographic temperature factors （B factor） of individual atoms contain important information about the thermal motion of the atoms in a macromolecule. Previously the theory of flexibility of active site has been established based on the observation that the enzyme activity is sensitive to low concentration denaturing agents. It has been found that the loss of enzyme activity occurs well before the disruption of the three-dimensional structural scaffold of the enzyme. To test the theory of conformational flexibility of enzyme active site, crystal structures were perturbed by soaking in low concentration guanidine hydrochloride solutions. It was found that many lysozyme crystals tested could still diffract until the concentration of guanidine hydrochloride reached 3 M. It was also found that the B factors averaged over individually collected data sets were more accurate. Thus it suggested that accurate measurement of crystal temperature factors could be achieved for medium-high or even medium resolution crystals by averaging over multiple data sets. Furthermore, we found that the correctly predicted active sites included not only the more flexible residues, but also some more rigid residues. Both the flexible and the rigid residues in the active site played an important role in forming the active site residue network, covering the majority of the substrate binding residues. Therefore, this experimental prediction method may be useful for characterizing the binding site and the function of a protein, such as drug targeting.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.51622201,91733301,and 61571015)
文摘Proteins are crucial to most biological processes, such as enzymes, and in various catalytic processes a dynamic motion is required. The dynamics of protein are embodied as a conformational change, which is closely related to the flexibility of protein. Recently, nanopore sensors have become accepted as a low cost and high throughput method to study the features of proteins. In this article, we used a SiN nanopore device to study the flexibility of T7 RNA polymerase（RNAP） and its complex with DNA promoter. By calculating full-width at half-maximum（FWHM） of Gaussian fits to the blockade histograms, we found that T7 RNAP becomes more flexible after binding DNA promoter. Moreover, the distribution of fractional current blockade suggests that flexibility alters due to a breath-like change of the volume.
文摘Understanding the conformational flexibility of the insulin drugs is of great importance for the treatment of diabetes mellitus. Once in the body, the drug must have a certain degree of mobility within a specified period of time for the manifestation of its pharmacological properties. This mobility ensures conformational states necessary for binding with the insulin receptor and activating specific biological processes. In this work we investigated conformational flexibility of the pharmacologically important insulin analogues—insulin lispro, insulin aspart, insulin glulisine, and insulin glargine, using the molecular dynamics simulation method. This study provides new insight into the nature of behaviour of A-and B-chains. It has been found out that B-chain substitutions result in rapid acting, while long-lasting action can be achieved by substitutions in both chains. The results of this study can be used for development of new insulin-based antidiabetic drugs.
