A novel three-dimensional holographic vector of atomic interaction field（3D-HoVAIF） was used to describe the chemical structures of 23 benzoxazinone derivatives as antithrombotic drugs.Here a quantitative structure ...A novel three-dimensional holographic vector of atomic interaction field（3D-HoVAIF） was used to describe the chemical structures of 23 benzoxazinone derivatives as antithrombotic drugs.Here a quantitative structure activity relationship（QSAR） model was built by partial least-squares（PLS） regression.The estimation stability and prediction ability of the model were strictly analyzed by both internal and external validations.The correlation coefficients of established PLS model,leave-one-out（LOO） cross-validation,and predicted values versus experimental ones of external samples were R2=0.899,RCV2=0.854 and Qext2=0.868,respectively.These values indicated that the built PLS model had both favorable estimation stability and good prediction capabilities.Furthermore,the satisfactory results showed that 3D-HoVAIF could preferably express the information related to the biological activity of benzoxazinone derivatives.展开更多
20 Typical flavonoids were selected for study on the interaction between them and PIM-1 kinase with the comparative molecular field analysis method（CoMFA） as well as the comparative molecular similarity index analys...20 Typical flavonoids were selected for study on the interaction between them and PIM-1 kinase with the comparative molecular field analysis method（CoMFA） as well as the comparative molecular similarity index analysis method（CoMSIA） based on molecule docking.3D-QSAR models between these flavonoids and receptor PIM-1 kinase were established.The obtained optimal cross-validation correlation coefficient Q2 for CoMFA model was 0.582,and the non-cross-validation correlation coefficient R2 was 0.955;the corresponding values for CoMSIA model were 0.790 and 0.974,respectively.These two models showed fairly fine stability and predictive ability.In addition,molecule docking results revealed the key residues in the receptor cavity and their specific action ways with flavonoids.展开更多
Based on the antitumor activity of chalcone derivatives and their structure, the structure-activity relationship of chalcone derivatives was analyzed by CoMFA (comparative molecular field analysis) method and then the...Based on the antitumor activity of chalcone derivatives and their structure, the structure-activity relationship of chalcone derivatives was analyzed by CoMFA (comparative molecular field analysis) method and then the 3D-QSAR (the three dimensional quantitative structures activity relationship) model was established. The analytical results showed that the model had good stability and prediction ability with cross-validated Q2 and non-cross-validated R2 values of 0.527 and 0.995, respectively. The contour map of the model explained the relationship between the structure of chalcone derivatives and antitumor activity, and could be analyzed to design antitumor chalcone derivatives. We designed some structure of chalcone derivatives and calculated their antitumor activity. In this paper, 24 chalcone derivatives were studied by CoMFA, 3D-QSAR, molecular design, which provided theoretical for designing good activities chalcone derivatives.展开更多
Flavonoids are endocrine disrupting compounds that occur ubiquitously in foods of plant origin.The Three-Dimensional Quantitative Structure-Activity Relationships (3D-QSAR) model based on ligand-receptor docking is es...Flavonoids are endocrine disrupting compounds that occur ubiquitously in foods of plant origin.The Three-Dimensional Quantitative Structure-Activity Relationships (3D-QSAR) model based on ligand-receptor docking is established between 20 flavonoids and estrogen receptor alpha (ERα),which may provide further theoretical basis for research on the relationship between flavones and estrogen.Comparative molecular field analysis (CoMFA) was employed and the best results of cross-validation and non cross validation were 0.845 and 0.988,respectively.Correspondingly,molecular similarity index analysis (CoMSIA) was employed and the results of cross-validation and non cross validation were 0.670 and 0.990,respectively.The CoMFA/CoMSIA and docking results reveal the structural features for estrogen activity and key amino acid residues in binding pocket,and provide an insight into the interaction between the ligands and these amino acid residues.展开更多
Based on the obtained data of half-lives（t1/2） for 31 polychlorinated biphenyl congeners（PCBs）, 3D quantitative structure-activity relationship（QSAR） pharmacophore was used to establish a 3D QSAR model to predic...Based on the obtained data of half-lives（t1/2） for 31 polychlorinated biphenyl congeners（PCBs）, 3D quantitative structure-activity relationship（QSAR） pharmacophore was used to establish a 3D QSAR model to predict the t1/2 values of the remaining 178 PCBs, using the structural parameters as independent variables and lgt1/2 values as the dependent variable. Among this process, the whole data set（31 compounds） was divided into a training set（24 compounds） for model generation and a test set（7 compounds） for model validation. Then, the full factor experimental design was used to research the potential second-order interactional effect between different substituent positions, obtaining the final regulation scheme for PCB. At last, a 3D QSAR pharmacophore model was established to validate the reasonable regulation targeting typical PCB with respect to half-lives and thermostability. As a result, the cross-validation correlation coefficient（q2） obtained by the 3D QSAR model was 0.845（〉0.5） and the coefficient of determination（r2） obtained was 0.936（〉0.9）, indicating that the models were robust and predictive. CoMSIA analyses upon steric, electrostatic and hydrophobic fields were 0.7%, 85.9%, and 13.4%, respectively. The electrostatic field was determined to be a primary factor governing the tt/2. From CoMSIA contour maps, tl/2 increased when substi- tuents possessed electropositive groups at the 2＇-, 3-, Y-, 5- and 5＇- positions and electronegative groups at the 3-, 3＇-, 5-, 6- and 6＇- positions, which could increase the PCB stability in transformer insulation oil. Modification of two typical PCB congeners（PCB-77 and PCB-81） showed that the lgtl/2 for three selected modified compounds increased by 13%（average ratio） compared with that of each congener and the thermostability of them were higher, validating the reasonability of the regulatory scheme obtained from the 3D QSAR model. These results are expected to be beneficial in predicting tl/2 values of PCB homologues and derivatives and in providing a theoretical foundation for further elucidation of the stability of PCBs.展开更多
基金supported by the Natural Science Foundation of Shaanxi Province (2009JQ2005)Foundation of Educational Commission of Shaanxi Province (09JK358) Graduate Innovation Fund of Shaanxi University of Science and Technology
文摘A novel three-dimensional holographic vector of atomic interaction field（3D-HoVAIF） was used to describe the chemical structures of 23 benzoxazinone derivatives as antithrombotic drugs.Here a quantitative structure activity relationship（QSAR） model was built by partial least-squares（PLS） regression.The estimation stability and prediction ability of the model were strictly analyzed by both internal and external validations.The correlation coefficients of established PLS model,leave-one-out（LOO） cross-validation,and predicted values versus experimental ones of external samples were R2=0.899,RCV2=0.854 and Qext2=0.868,respectively.These values indicated that the built PLS model had both favorable estimation stability and good prediction capabilities.Furthermore,the satisfactory results showed that 3D-HoVAIF could preferably express the information related to the biological activity of benzoxazinone derivatives.
基金Sponsored by the National Natural Science Foundation of China (No. 20737001,20977046)the National Basic Research Program of China (No. 2009CB42160-4)
文摘20 Typical flavonoids were selected for study on the interaction between them and PIM-1 kinase with the comparative molecular field analysis method（CoMFA） as well as the comparative molecular similarity index analysis method（CoMSIA） based on molecule docking.3D-QSAR models between these flavonoids and receptor PIM-1 kinase were established.The obtained optimal cross-validation correlation coefficient Q2 for CoMFA model was 0.582,and the non-cross-validation correlation coefficient R2 was 0.955;the corresponding values for CoMSIA model were 0.790 and 0.974,respectively.These two models showed fairly fine stability and predictive ability.In addition,molecule docking results revealed the key residues in the receptor cavity and their specific action ways with flavonoids.
文摘Based on the antitumor activity of chalcone derivatives and their structure, the structure-activity relationship of chalcone derivatives was analyzed by CoMFA (comparative molecular field analysis) method and then the 3D-QSAR (the three dimensional quantitative structures activity relationship) model was established. The analytical results showed that the model had good stability and prediction ability with cross-validated Q2 and non-cross-validated R2 values of 0.527 and 0.995, respectively. The contour map of the model explained the relationship between the structure of chalcone derivatives and antitumor activity, and could be analyzed to design antitumor chalcone derivatives. We designed some structure of chalcone derivatives and calculated their antitumor activity. In this paper, 24 chalcone derivatives were studied by CoMFA, 3D-QSAR, molecular design, which provided theoretical for designing good activities chalcone derivatives.
基金supported by the National High Technology Research and Development Program of China (Grant No. 2006AA06Z424)the National Natural Science Foundation of China (Grant No. 20737001)
文摘Flavonoids are endocrine disrupting compounds that occur ubiquitously in foods of plant origin.The Three-Dimensional Quantitative Structure-Activity Relationships (3D-QSAR) model based on ligand-receptor docking is established between 20 flavonoids and estrogen receptor alpha (ERα),which may provide further theoretical basis for research on the relationship between flavones and estrogen.Comparative molecular field analysis (CoMFA) was employed and the best results of cross-validation and non cross validation were 0.845 and 0.988,respectively.Correspondingly,molecular similarity index analysis (CoMSIA) was employed and the results of cross-validation and non cross validation were 0.670 and 0.990,respectively.The CoMFA/CoMSIA and docking results reveal the structural features for estrogen activity and key amino acid residues in binding pocket,and provide an insight into the interaction between the ligands and these amino acid residues.
文摘Based on the obtained data of half-lives（t1/2） for 31 polychlorinated biphenyl congeners（PCBs）, 3D quantitative structure-activity relationship（QSAR） pharmacophore was used to establish a 3D QSAR model to predict the t1/2 values of the remaining 178 PCBs, using the structural parameters as independent variables and lgt1/2 values as the dependent variable. Among this process, the whole data set（31 compounds） was divided into a training set（24 compounds） for model generation and a test set（7 compounds） for model validation. Then, the full factor experimental design was used to research the potential second-order interactional effect between different substituent positions, obtaining the final regulation scheme for PCB. At last, a 3D QSAR pharmacophore model was established to validate the reasonable regulation targeting typical PCB with respect to half-lives and thermostability. As a result, the cross-validation correlation coefficient（q2） obtained by the 3D QSAR model was 0.845（〉0.5） and the coefficient of determination（r2） obtained was 0.936（〉0.9）, indicating that the models were robust and predictive. CoMSIA analyses upon steric, electrostatic and hydrophobic fields were 0.7%, 85.9%, and 13.4%, respectively. The electrostatic field was determined to be a primary factor governing the tt/2. From CoMSIA contour maps, tl/2 increased when substi- tuents possessed electropositive groups at the 2＇-, 3-, Y-, 5- and 5＇- positions and electronegative groups at the 3-, 3＇-, 5-, 6- and 6＇- positions, which could increase the PCB stability in transformer insulation oil. Modification of two typical PCB congeners（PCB-77 and PCB-81） showed that the lgtl/2 for three selected modified compounds increased by 13%（average ratio） compared with that of each congener and the thermostability of them were higher, validating the reasonability of the regulatory scheme obtained from the 3D QSAR model. These results are expected to be beneficial in predicting tl/2 values of PCB homologues and derivatives and in providing a theoretical foundation for further elucidation of the stability of PCBs.
