检索结果-南通市图书馆

中国化学会第十二届全国量子化学会议

作者： Xiuchan Xiao Xiaojun Zeng Juanjuan Sun xuemei pu Menglong Li 四川大学

Theβ2 adrenergic receptor（β2AR）constitutes the largest class of both human membrane proteins and drug *** conformational change from an inactive state to an active state enables the receptor to transmit a signal from the extracellular ligand-binding site to an intracellular G protein,thereby initiating diverse intracellular signaling ***,the activation mechanism has been not ***,we used target molecular dynamics simulations（TMD）to investigate the activation mechanism ofβ2AR from the inactive to the active *** simulations were performed from the inactive state to the active with different restraint *** results show that the transition begins from the conformational changes of the extracellular region close to the ligand-binding site then to the G-protein-binding *** G-protein-binding site usually adopted an intermediate conformation substantially different from crystallographic conformations of active and inactive *** activation,the Lys305-Asp192 salt bridge formed between ECL3 and ECL2becomes unstable and is finally *** end of helix 7 adopts a distortedα-helical conformation,and helix 3 moves apart from helix 6 with Tyr326 losing contact with helix *** results also indicate that the comprised multiple receptor conformations have different implications for signal transition.

关键词：

来源： cnki会议评论

在线全文

cnki会议

学校读者我要写书评

暂无评论

Shining Light on Mechanism for Odor-selectivity of CNT-immobilized Olfactory Receptor

Shining Light on Mechanism for Odor-selectivity of CNT-immob...

引用

中国化学会第十三届全国分析化学年会

作者： Liyun Zhang Jiangfan Chen Fuhui Zhang Menglong Li xuemei pu College of Chemistry Sichuan University

Olfactory receptor（OR）-based bioelectronics nose is a new type of bio-affinity sensor applied for detecting numerous odorant molecules. In order to elucidate the effect of the adsorption of nanomaterial carriers on the receptor structure and its selectivity to odors, we used a systematic computation-scheme to study two OR models immobilized onto carbon nanotube. Our result indicates that there is a multistep OR-adsorption process driven by hydrophobic interaction. Many allosteric communication pathways exist between the absorbed residues and the pocket ones, leading to a significant shrinkage of the pocket. Consequently, the size-selectivity of the receptor to the odors is changed to some extent. But, the odor size and its hydrophobicity, rather than specific functional groups of the odor, still play a determinant role in binding OR, at least for the 132 odors under study. Regardless of the limitation for the odor size in initial recognition, the different-size odors could induce significant changes in the pocket conformation so that it could better match the pocket space, indicating the importance of the ligand-fit binding. Due to the CNT-induced shrinkage of the pocket, the CNT immobilization could increase the binding affinity through enhancing van der Wan interaction, in particular for the large odors.

关键词： Olfactory receptor(OR) Carbon Nanotube Adsorption Selectivity

来源： cnki会议评论

在线全文

cnki会议

学校读者我要写书评

暂无评论

Molecular mechanism of carbon nanotube to activate Subtilisin Carlsberg in polar and non-polar organic media

Molecular mechanism of carbon nanotube to activate Subtilisi...

引用

第十三届全国量子化学会议

作者： Liyun Zhang Xi zhang Yuanyuan Jiang Anming Tian xuemei pu College of Chemistry Sichuan University

Enzyme immobilization has been used in non-aqueous enzymatic catalysis due to its advantages like enhancing stability, activity, and recycle rate. Thus, in the work, we mainly used molecular dynamics(MD) simulation and protein structure network(PSN) to study subtilisin Carlsberg(SC) immobilized onto carbon nanotube(CNT) in water, acetonitrile and heptane solvents, in order to explore activation mechanism of enzymes in non-aqueous *** result indicates that the affinity of SC with CNT follows the decreasing order of water >acetonitrile > heptane. the distances between two β-strands of substrate-binding pocket are significantly expanded by the immobilization in the increasing order of water < acetonitrile

关键词： non-aqueous enzymatic catalysis immobilization carbon nanotube MD PSN

来源： cnki会议评论

在线全文

cnki会议

学校读者我要写书评

暂无评论

Versatile chiroptical induction/manipulation through specific solvation of ion pairs by alcohols

引用

Science China Chemistry 2024年

作者： Chunhong Liu Xin Chen Yanling Shen Ting Zhao Dayang Zhou Kun Li Jiecheng Ji Wanhua Wu xuemei pu Cheng Yang Key Laboratory of Green Chemistry & Technology of Ministry of Education Sichuan University Comprehensive Analysis Center ISIR Osaka University

While extensive research has explored manipulating supramolecular chirality through internal and external factors, the specific solvation effect remains uncharted territory. This study synthesized ortho-functionalized pillar[5]arene（P[5]） derivatives Mn and Dn via thiol-Michael addition, characterizing them through spectroscopic and X-ray single-crystal analyses. Mn and Dn interacted with chiral amines, yielding significant circular dichroism（CD） responses. Intriguingly, the chiral induction exhibited pronounced specific solvation effects, where achiral alcohols either enhanced, attenuated, or reversed CD signals. Testing over40 alcohols revealed correlations between the specific solvation effects and alcohol polarity and acidity. Molecular dynamics simulations unveiled that the alcohol interacted distinctly through hydrogen bonding, with one ion pair bonding up to four alcohol molecules. The Rp-and Sp-preference of the P[5] core could be altered by the number of bonded alcohols. This work uncovers the critical role of alcohol-specific solvation in ion pair-involved chiral assembly, pertinent for asymmetric ion-pairing catalysis and the use of alcohol additives in organic solvents.

关键词：

来源：

同方期刊数据库评论

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Exploring the activation mechanism of carbon nanotube on Subtilisin Carlsberg in organic media via molecular dynamics simulation

Exploring the activation mechanism of carbon nanotube on Sub...

引用

中国化学会第30届学术年会-第十九分会：化学中的量子与经典动力学

作者： Liyun Zhang Xiuchan Xiao Xi zhang Yihuan Zhao Yuanyuan Jiang xuemei pu Faculty of Chemistry Sichuan University

Enzyme immobilization has been used in non-aqueous enzymatic catalysis due to its advantages like enhancing stability, activity, and recycle rate. Subtilisin Carlsberg(SC), as a member of the serine protease class, is particularly pronounced in this field. However, the immobilization details and activation mechanism have not been clearly elucidated on experiments. Thus, in the work, we used molecular dynamics(MD) simulation and protein structure network(PSN) to study SC immobilized onto carbon nanotube(CNT) in three different-polar media(viz., aqueous, acetonitrile, and heptane) in order to address these questions above. The result indicate that SC has stronger affinity with CNT in aqueous solvent than in organic media due to more adsorbed atoms and larger contact area, which should stem from the competitive effect between absorbed residues and organic molecules with CNT. The result from the binding energy between SC and substrate indicates that the immobilized SC has higher affinity with substrate compared to free enzymes in all three media. The distances between two β-strands(Gly100-Tyr103, and Ser125-Gly128) in the binding pocket are expended by the immobilization, which should favor substrate-binding and contribute to the experiment findings that the enzyme could improve its catalytic activity by means of immobilization. The PSN analysis reveals that the immobilization could stabilize the structures of the binding pockets through the structure communication networks beginning at the binding residues with CNT while, the free enzymes in the three media present significant variations in the pocket structures due to the effects of the organic solvents. The communication pathway to the catalytic site starts from F261, and then passes through oxyanion-hole residue N155, and finally ends in S221 in aqueous solvent, which is different from the pathways in the two organic media. However, the organic solvent and CNT do not present observable effects on the catalytic cente

关键词： non-aqueous enzymatic catalysis immobilization carbon nanotube molecular dynamics simulation

来源： cnki会议 cnki会议评论

在线全文

学校读者我要写书评

暂无评论

Study on mechanism of mutation-caused constitutive activity of GPCR via molecular dynamics simulation

Study on mechanism of mutation-caused constitutive activity ...

引用

第十三届全国量子化学会议

作者： Nan Gao Tao Liang Yanzhi Guo Menglong Li Anmin Tian xuemei pu College of Chemistry Sichuan University

G-protein-coupled receptors(GPCRs) are important drug targets, which are in general activated by ligands and deliver signal to cytosolic part. Nevertheless, the mechanisms of constitutively active mutants(CAMs) have been unclear on ***, we used microsecond time-scale molecular dynamics simulations to study the effect of an important F282L mutation on β2AR. With the aid of the principle component analysis and the correlation analysis, our results revealed that F282L mutation could increase instability of the overall structure, cause dramatic fluctuation of NPxxY and extracellular loops, and decrease restraining of helices through weakening the interhelical H-bonding,which should contribute to the constitutive activity reported by the experiments. In addition,using the protein structure network(PSN) method, we found that the mutant exhibits less information flows comparing to the wild β2AR. Furthermore, the mutation weakens the role of TM6 in taking part in the signal transmission but enhances the impact of TM3. In addition,the results from virtual screening reveals that similar to the active state of β2AR, the mutant exhibits higher enrichment factor for the agonists than the inverse agonists, indicating that the F282L mutation advances the activation of β2AR. In a whole, our observations provide valuable information for understanding the mechanism of the mutation-caused constitutive activity of GPCR and related drug-design.

关键词： G-protein coupled receptor molecular dynamics simulations mutation constitutive activity protein structure network

来源： cnki会议 cnki会议评论

在线全文

学校读者我要写书评

暂无评论

Understanding the mechanism of activation/deactivation of GLP-1R via accelerated molecular dynamics simulation

Understanding the mechanism of activation/deactivation of GL...

引用

2019中国化学会第十五届全国计算（机）化学学术会议

作者： Xiuchan Xiao Miao Qin Yaqi Ren Qianglin Li Zheng Zhou xuemei pu School of Material Science and Environmental Engineering Chengdu Technological University Center of Big Data for Smart Environmental Protection Chengdu Technological University School of Chemistry Sichuan University

Glucagon-like peptide-1 receptor（GLP-1 R）, as a member of the class B G protein-coupled receptors（GPCRs）, plays a crucial role in regulating blood glucose level signal recognition through their activation. The conformation transition in the activation pathway is particular importance for its function. To investigate the activation mechanism of GLP-1 R, the crystal structures of active and inactive are chosen to perform a total 2 μs of accelerated molecular dynamics（a MD） simulations and 400 ns conventional molecular dynamics（c MD） simulations. With the aid of structural analysis and potential of mean force（PMF）, we revealed the role of different helices in activation and deactivation process and obtained the intermediate states during activation and deactivation that are difficult to capture in experiments. Protein structure network（PSN） was utilized to clarify the allosteric communication pathways of activation and deactivation and reveal the mechanisms of its activation and deactivation. The observations from the work could advance our understanding of the activation mechanism of GLP-1 R and related drug design.

关键词： GPCR accelerated molecular dynamics activation deactivation

来源： cnki会议评论

在线全文

cnki会议

学校读者我要写书评

暂无评论

1,2,4,5-四嗪含氮取代基衍生物结构和性质的理论研究

引用

有机化学 2011年第3期31卷 328-335页

作者：梁晓琴蒲雪梅田安民四川师范大学化学与材料科学学院成都610068 四川大学化学学院成都610064

在B3LYP/aug-cc-pvDZ理论水平上研究了CN,NO2,NH2,N3,N2H,NHNH2,N4H和N4H3含氮取代基取代1,2,4,5-四嗪环上的两个氢原子生成的衍生物,预测了它们的分子构型、分解能及含能性质.对衍生物分解能的研究结果表明,CN取代的衍生物的分解能比... 详细信息

在B3LYP/aug-cc-pvDZ理论水平上研究了CN,NO2,NH2,N3,N2H,NHNH2,N4H和N4H3含氮取代基取代1,2,4,5-四嗪环上的两个氢原子生成的衍生物,预测了它们的分子构型、分解能及含能性质.对衍生物分解能的研究结果表明,CN取代的衍生物的分解能比未取代时更高,而其余基团的取代使分解能降低.生成热的研究显示取代基化合物的生成热越大,取代1,2,4,5-四嗪中的氢原子后生成衍生物的生成热也越大;CN,N3和N4H取代的1,2,4,5-四嗪衍生物的单位原子生成热在83.1～95.2 kJ,比文献报道的三叠氮基—均三嗪的(70.2 kJ)更高;N4H,N3,N4H3,N2H和CN取代的1,2,4,5-四嗪衍生物,生成热在904.9～1496.6 kJ·mol-1,但N4H和N4H3取代的衍生物分解能较小,稳定性较差.

关键词：高能量密度物质 1,2,4,5-四嗪含氮取代基分解能生成热

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Probing Druggability on Interface and its Allosteric Regulation Mechanism on Drug Screening for CXCR4 Homodimer

Probing Druggability on Interface and its Allosteric Regulat...

引用

2019中国化学会第十五届全国计算（机）化学学术会议

作者： Liting Shen 陈建芳 Xingyu Du Yanzhi Guo Menglong Li xuemei pu College of Chemistry Sichuan University 四川大学

Modulating protein-protein interactions（PPIs） with small drug-like molecules targeting it exhibits great promising in modern drug discovery. G protein-coupled receptors（GPCRs） are the largest family of targeted proteins and could form dimers in living biological cells through PPIs. However, compared to drug development of the orthosteric site, there has been lack of investigations on the druggability of the PPI interface for GPCRs and its functional implication on experiments. Thus, in order to address these issues, we constructed a novel computational strategy, which involved in molecular dynamics simulation, virtual screening and protein structure network（PSN）, to study one representative GPCR homodimer（CXCR4）. One druggable pocket was identified in the PPI interface and one small molecule targeting it was screened, which could strengthen PPI mainly through hydrophobic interaction between the benzene rings of the PPI molecule and TM4 of the receptor. The PSN results further reveals that the PPI molecule could increase the number of the allosteric regulation pathways between the druggable pocket of the dimer interface to the orthostatic site for the subunit A but only play minor role for the other subunit B, leading to the asymmetric change in the volume of the binding pockets for the two subunits（increase for the subunit A and minor change for the subunit B）. Consequently, the screening performance of the subunit A to the antagonists is enhanced while the subunit B is unchanged nearly, implying that the PPI molecule may be beneficial to enhance the drug efficacies of the antagonists. In addition, one main regulation pathway with the highest frequency was identified for the subunit A, which consists of Trp1955.34-Tyr190 ECL2-Val1965.35-Gln2005.39-Asp2626.58-Cys28 N-term, revealing their importance in the allosteric regulation from the PPI molecule. The observations from the work could provide valuable information for the development of the PPI drug-like molecule fo

关键词： Target GPCR dimer interface druggability regulation mechanism computation

来源： cnki会议评论

在线全文

cnki会议

学校读者我要写书评

暂无评论

Exploring Activation Mechanism Induced by Glutamate for one Homodimer of Class C GPCRs via Molecular Dynamics Simulation

Exploring Activation Mechanism Induced by Glutamate for one ...

引用

2019中国化学会第十五届全国计算（机）化学学术会议

作者： Ting Lei 张福会 Nian Xu Zhenxin Hu Menglong Li xuemei pu College of Chemistry Sichuan University 四川大学

Metabotropic glutamate receptors of class C GPCRs exist as constitutive dimers, which play important roles in activating excitatory synapses of the central nerve system. However, due to lack of crystal structures and complicated cell environment, the activation mechanism induced by agonists has not been clarified on experiments. To address the problem, we used microsecond allatom molecular dynamics（MD） simulation couple with protein structure network（PSN） to explore the glutamate-induced activation for the mGluR1 homodimer. The results indicate that the glutamate binding stabilizes not only the closure of venus flytrap domains but also the polar interaction of LB2-LB2, in turn keeping the extracelluar domain in the active state. The activation of the excelluar domain drives TMDs closer and induces aymmetric activation for the TMD domains of the two protomers. One protomer with lower binding energy between the agonist and its extracelluar is activated while the other one with higher binding energy is still in the inactive state. The asymmetric ligand-binding and TMD activation between the two protomers should be common features for the GPCR homodimers, either the class A or the class C. PSN identify the allostrical regulation pathway from the ligand-binding pocket in the extracellur domain to the G-protein binding site in the intracellur TMD region, and further reveals that the combination of trans-activation and cisactivation triggers one protomer to be activated. These observations could provide valuable molecular information for understanding of the structure and the implication in drug efficacy for the class C GPCR dimers.

关键词： Metabotropic glutamate receptor 1 dimer ligand activation mechanism molecular dynamics simulation protein structure network

来源： cnki会议评论

在线全文

cnki会议

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：