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
It is important to calibrate micro-parameters for applying partied flow code(PFC)to study mechanical characteristics and failure mechanism of rock materials.Uniform design method is firstly adopted to determine the mi...It is important to calibrate micro-parameters for applying partied flow code(PFC)to study mechanical characteristics and failure mechanism of rock materials.Uniform design method is firstly adopted to determine the microscopic parameters of parallel-bonded particle model for three-dimensional discrete element particle flow code(PFC3D).Variation ranges of microscopic of the microscopic parameters are created by analyzing the effects of microscopic parameters on macroscopic parameters(elastic modulus E,Poisson ratio v,uniaxial compressive strengthσc,and ratio of crack initial stress to uniaxial compressive strengthσci/σc)in order to obtain the actual uniform design talbe.The calculation equations of the microscopic and macroscopic parameters of rock materials can be established by the actual uniform design table and the regression analysis and thus the PFC3D microscopic parameters can be quantitatively determined.The PFC3D simulated results of the intact and pre-cracked rock specimens under uniaxial and triaxial compressions(including the macroscopic mechanical parameters,stress−strain curves and failure process)are in good agreement with experimental results,which can prove the validity of the calculation equations of microscopic and macroscopic parameters.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
目的对23个四氢-咪唑-苯二氮酮(TIBO)类抗艾滋病药物分子进行定量构效关系(QSAR)研究。方法采用本实验室新近提出的三维全息原子场作用矢量(3D-HoVAIF)表征TIBO类抗艾滋病药物分子结构。然后运用偏最小二乘回归(partial least square re...目的对23个四氢-咪唑-苯二氮酮(TIBO)类抗艾滋病药物分子进行定量构效关系(QSAR)研究。方法采用本实验室新近提出的三维全息原子场作用矢量(3D-HoVAIF)表征TIBO类抗艾滋病药物分子结构。然后运用偏最小二乘回归(partial least square regression,PLS)建立3D-HoVAIF描述符与TIBO类抗艾滋病药物活性之间的QSAR模型。结果用此方法建模的复相关系数(R2cum)、交互校验复相关系数(Q2cum)和模型的标准偏差(SD)分别为R2cum=0.824,Q2cum=0.778与SD=0.56,均优于文献值。结论3D-HoVAIF能较好表征TIBO类抗艾滋病药物分子结构信息,因而能建立具有良好稳定性和预测能力的QSAR模型。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
The quantitative structure-activity relationship (QSAR) of 30 acylthiourea analogues was studied by using a three-dimensional holographic vector of atomic interaction field (3D-HoVAIF) to describe their chemical s...The quantitative structure-activity relationship (QSAR) of 30 acylthiourea analogues was studied by using a three-dimensional holographic vector of atomic interaction field (3D-HoVAIF) to describe their chemical structures. The descriptors obtained were screened by stepwise multiple regression (SMR) and a partial least-squares (PLS) regression model was built. The correlation coefficient r^2 of the established model and Leave-One-Out (LOO) Cross-Validation (CV) correlation coefficient q^2 are 0.624 and 0.409, respectively. The model has favorable stability and good prediction capability, and further QSAR analysis showed that hydrophobic interaction has the most important effect on the activity of acylthiourea analogue and 3D-HoVAIF was applicable to the molecular structural characterization and biologicalactivity prediction.展开更多
A three-dimensional quantitative structure-activity relationship(3 D-QSAR) study was conducted to analyze the A1 AR density(Bmax) of 56 3-aroyl-5-substituted thiophene derivatives(ASTDs) in human A1 Chinese hamster ov...A three-dimensional quantitative structure-activity relationship(3 D-QSAR) study was conducted to analyze the A1 AR density(Bmax) of 56 3-aroyl-5-substituted thiophene derivatives(ASTDs) in human A1 Chinese hamster ovary(hA1 CHO) membranes by the comparative molecular field analysis(CoMFA) method. A training set of 45 compounds was used to establish the predictive model, which was verified by the test set of 17 compounds containing template molecule and 5 newly designed molecules. The cross-validation(R2 cv) and non-cross-validation(R2) coefficients of the training set were 0.655 and 0.959, respectively. The model was used to predict the activities of the compounds of the training and test sets, and the results indicated that the models had strong stability and good prediction ability. According to model analysis, the contribution of steric and electrostatic fields was 51.4% and 48.6%, respectively. Based on the 3 D contour maps, five excellent ASTDs agonists were designed, which need to be further verified by biomedical experiments.展开更多
Topomer comparative molecular field analysis(Topomer Co MFA)and holographic quantitative structure-activity relationship(HQSAR)for 1302,5-diketopiperazine derivatives were used to build a three-dimensional quantitativ...Topomer comparative molecular field analysis(Topomer Co MFA)and holographic quantitative structure-activity relationship(HQSAR)for 1302,5-diketopiperazine derivatives were used to build a three-dimensional quantitative structure-activity relationship(3D-QSAR)model.The results show that the models have high predictive ability.For Topomer CoMFA,the cross-validated q^2 value is 0.710 and the non-cross-validated r^2 value is 0.834.The most effective HQSAR model shows that the cross-validation q^2 value is 0.700,the non-cross-validated r^2 value is 0.815,and the best hologram length value is 353 using connections and bonds as fragment distinctions.50 highly active 2,5-diketopiperazine derivatives were designed based on the three-dimensional equipotential map and HQSAR color code map.Finally,the molecular docking method was also used to study the interactions of these new molecules by docking the ligands into the diketopiperazine active site,which revealed the likely bioactive conformations.This study showed that there are extensive interactions between the new molecule and Arg156,Arg122 residues in the active site of diketopiperazine.These results provide useful insights for the design of potent of the new 2,5-diketopiperazine derivatives.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Projects(51474251,51874351)supported by the National Natural Science Foundation,China。
文摘It is important to calibrate micro-parameters for applying partied flow code(PFC)to study mechanical characteristics and failure mechanism of rock materials.Uniform design method is firstly adopted to determine the microscopic parameters of parallel-bonded particle model for three-dimensional discrete element particle flow code(PFC3D).Variation ranges of microscopic of the microscopic parameters are created by analyzing the effects of microscopic parameters on macroscopic parameters(elastic modulus E,Poisson ratio v,uniaxial compressive strengthσc,and ratio of crack initial stress to uniaxial compressive strengthσci/σc)in order to obtain the actual uniform design talbe.The calculation equations of the microscopic and macroscopic parameters of rock materials can be established by the actual uniform design table and the regression analysis and thus the PFC3D microscopic parameters can be quantitatively determined.The PFC3D simulated results of the intact and pre-cracked rock specimens under uniaxial and triaxial compressions(including the macroscopic mechanical parameters,stress−strain curves and failure process)are in good agreement with experimental results,which can prove the validity of the calculation equations of microscopic and macroscopic parameters.
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.
文摘目的对23个四氢-咪唑-苯二氮酮(TIBO)类抗艾滋病药物分子进行定量构效关系(QSAR)研究。方法采用本实验室新近提出的三维全息原子场作用矢量(3D-HoVAIF)表征TIBO类抗艾滋病药物分子结构。然后运用偏最小二乘回归(partial least square regression,PLS)建立3D-HoVAIF描述符与TIBO类抗艾滋病药物活性之间的QSAR模型。结果用此方法建模的复相关系数(R2cum)、交互校验复相关系数(Q2cum)和模型的标准偏差(SD)分别为R2cum=0.824,Q2cum=0.778与SD=0.56,均优于文献值。结论3D-HoVAIF能较好表征TIBO类抗艾滋病药物分子结构信息,因而能建立具有良好稳定性和预测能力的QSAR模型。
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.
基金supported by the National High-tech Research Program (the "863" Program, No. 2006AA02Z312)Innovative Group Program for Graduates of Chongqing University, Science and Innovation Fund (No. 200711C1A0010260)
文摘The quantitative structure-activity relationship (QSAR) of 30 acylthiourea analogues was studied by using a three-dimensional holographic vector of atomic interaction field (3D-HoVAIF) to describe their chemical structures. The descriptors obtained were screened by stepwise multiple regression (SMR) and a partial least-squares (PLS) regression model was built. The correlation coefficient r^2 of the established model and Leave-One-Out (LOO) Cross-Validation (CV) correlation coefficient q^2 are 0.624 and 0.409, respectively. The model has favorable stability and good prediction capability, and further QSAR analysis showed that hydrophobic interaction has the most important effect on the activity of acylthiourea analogue and 3D-HoVAIF was applicable to the molecular structural characterization and biologicalactivity prediction.
基金supported by the National Natural Science Foundation of China (21676292,21075138)special fund of State Key Laboratory of Structure Chemistry (2016028)。
文摘A three-dimensional quantitative structure-activity relationship(3 D-QSAR) study was conducted to analyze the A1 AR density(Bmax) of 56 3-aroyl-5-substituted thiophene derivatives(ASTDs) in human A1 Chinese hamster ovary(hA1 CHO) membranes by the comparative molecular field analysis(CoMFA) method. A training set of 45 compounds was used to establish the predictive model, which was verified by the test set of 17 compounds containing template molecule and 5 newly designed molecules. The cross-validation(R2 cv) and non-cross-validation(R2) coefficients of the training set were 0.655 and 0.959, respectively. The model was used to predict the activities of the compounds of the training and test sets, and the results indicated that the models had strong stability and good prediction ability. According to model analysis, the contribution of steric and electrostatic fields was 51.4% and 48.6%, respectively. Based on the 3 D contour maps, five excellent ASTDs agonists were designed, which need to be further verified by biomedical experiments.
基金supported by the National Natural Science Funds of China(21475081)the Natural Science Foundation of Shaanxi Province(2019JM-237)the Graduate Innovation Fund of Shaanxi University of Science and Technology。
文摘Topomer comparative molecular field analysis(Topomer Co MFA)and holographic quantitative structure-activity relationship(HQSAR)for 1302,5-diketopiperazine derivatives were used to build a three-dimensional quantitative structure-activity relationship(3D-QSAR)model.The results show that the models have high predictive ability.For Topomer CoMFA,the cross-validated q^2 value is 0.710 and the non-cross-validated r^2 value is 0.834.The most effective HQSAR model shows that the cross-validation q^2 value is 0.700,the non-cross-validated r^2 value is 0.815,and the best hologram length value is 353 using connections and bonds as fragment distinctions.50 highly active 2,5-diketopiperazine derivatives were designed based on the three-dimensional equipotential map and HQSAR color code map.Finally,the molecular docking method was also used to study the interactions of these new molecules by docking the ligands into the diketopiperazine active site,which revealed the likely bioactive conformations.This study showed that there are extensive interactions between the new molecule and Arg156,Arg122 residues in the active site of diketopiperazine.These results provide useful insights for the design of potent of the new 2,5-diketopiperazine derivatives.