With the artificial neural network（ANN） method combined with the multiple linear regression（MLR）,based on a series of quantum chemical descriptors and molecular connectivity indexes,quantitative structure-activity...With the artificial neural network（ANN） method combined with the multiple linear regression（MLR）,based on a series of quantum chemical descriptors and molecular connectivity indexes,quantitative structure-activity relationship（QSAR） models to predict the acute toxicity（-lgEC50） of substituted aromatic compounds to Photobacterium phosphoreum were established.Four molecular descriptors that appear in the MLR model,namely,the second order valence molecular connectivity index（2XV）,the energy of the highest occupied molecular orbital（EHOMO）,the logarithm of n-octyl alcohol/water partition coefficient（logKow） and the Connolly molecular area（MA）,were inputs of the ANN model.The root-mean-square error（RMSE） of the training and validation sets of the ANN model are 0.1359 and 0.2523,and the correlation coefficient（R） is 0.9810 and 0.8681,respectively.The leave-one-out（LOO） cross validated correlation coefficient（Q L2OO） of the MLR and ANN models is 0.6954 and 0.6708,respectively.The result showed that the two methods are complementary in the calculations.The regression method gave support to the neural network with physical explanation,and the neural network method gave a more accurate model for QSAR.In addition,some insights into the structural factors affecting the acute toxicity and toxicity mechanism of substituted aromatic compounds were discussed.展开更多
The pathogenesis of Alzheimer’s disease (AD) putatively involves a compromised blood-brain barrier (BBB). In particular, the importance of brain-to-blood transport of brain-derived metabolites across the BBB has gain...The pathogenesis of Alzheimer’s disease (AD) putatively involves a compromised blood-brain barrier (BBB). In particular, the importance of brain-to-blood transport of brain-derived metabolites across the BBB has gained increasing attention as a potential mechanism in the pathogenesis of neurodegenerative disorders such as AD, which is characterized by the aberrant polymerization and accumulation of specific misfolded proteins, particularly β-amyloid (Aβ), a neuropathological hallmark of AD. P-glycoprotein (P-gp), a major component of the BBB, plays a role in the etiology of AD through Aβ clearance from the brain. Our QSAR models on a series of purine-type and propafenone-type substrates of P-gp showed that the interaction between P-gp and its modulators depended on Molar Refractivity, LogP, and Shape Attribute of drugs it transports. Meanwhile, another model on BBB partitioning of some compounds revealed that BBB partitioning relied upon the polar surface area, LogP, Balaban Index, the strength of a molecule combined with the membrane-water complex, and the changeability of the structure of a solute-membrane-water complex. The predictive model on BBB partitioning contributes to the discovery of some molecules through BBB as potential AD therapeutic drugs. Moreover, the interaction model of P-gp and modulators for treatment of multidrug resistance (MDR) indicates the discovery of some molecules to increase Aβ clearance from the brain and reduce Aβ brain accumulation by regulating BBB P-gp in the early stages of AD. The mechanism provides a new insight into the therapeutic strategy for AD.展开更多
Quantitative structure-biodegradability relationships （QSBRs） were established to develop predictive models and mechanistic explanations for acid dyestuffs as well as biological activities. With a total of four desc...Quantitative structure-biodegradability relationships （QSBRs） were established to develop predictive models and mechanistic explanations for acid dyestuffs as well as biological activities. With a total of four descriptors, molecular weight （MW）, energies of the highest occupied molecular orbital （EHOMO）, the lowest unoccupied molecular orbital （ELUMO）, and the excited state （EES）, calculated using quantum chemical semi-empirical methodology, a series of models were analyzed between the dye biodegradability and each descriptor. Results showed that EHOMO and Mw were the dominant parameters controlling the biodegradability of acid dyes. A statistically robust QSBR model was developed for all studied dyes, with the combined application of EHOMO and Mw. The calculated biodegradations fitted well with the experimental data monitored in a facultative-aerobic process, indicative of the reliable prediction and mechanistic character of the developed model.展开更多
The genotoxicity of 22 substituted nitrobenzenes were evaluated by the chromosome aberrations test in in vitro human peripheral lymphocytes.18 of 22 compounds exhibit genotoxic activities.Quantitative structure-activi...The genotoxicity of 22 substituted nitrobenzenes were evaluated by the chromosome aberrations test in in vitro human peripheral lymphocytes.18 of 22 compounds exhibit genotoxic activities.Quantitative structure-activity relationship model was established to correlate the genotoxicity of substituted nitrobenzenes with the characteristics of the substituents on benzene ring.展开更多
Carotenoids are a family of effective active oxygen scavengers, which can reduce the danger of occurrence of chronic diseases such as cardiovascular disease, cataract, cancer, and so on. The quantitative structure-act...Carotenoids are a family of effective active oxygen scavengers, which can reduce the danger of occurrence of chronic diseases such as cardiovascular disease, cataract, cancer, and so on. The quantitative structure-activity relationship （QSAR） equation between carotenoids and antioxidant activity was established by quantum chemistry AM1, molecular mechanism （MM＋） and stepwise regression analysis methods, and the model was evaluated by leave-one-out approach. The results showed that the significant molecular descriptors related to the antioxidant activity of carotenoids were the energy difference （E_HL） between the lowest unoccupied molecular orbital （LUMO） and the highest occupied molecular orbital （HOMO） and ionization energy （Eiso）. The model showed a good predictive ability （Q^2 〉 0.5）.展开更多
A new set of descriptors, HSEHPCSV （component score vector of hydrophobic, steric, and electronic properties together with hydrogen bonding contributions）, were derived from principal component analyses of 95 physic...A new set of descriptors, HSEHPCSV （component score vector of hydrophobic, steric, and electronic properties together with hydrogen bonding contributions）, were derived from principal component analyses of 95 physicochemical variables of 20 natural amino acids separately according to different kinds of properties described, namely, hydrophobic, steric, and electronic properties as well as hydrogen bonding contributions. HSEHPCSV scales were then employed to express structures of angiotensin-converting enzyme inhibitors, bitter tasting thresholds and bactericidal 18 peptide, and to construct QSAR models based on partial least square （PLS）. The results obtained are as follows： the multiple correlation coefficient （R2cum） of 0.846, 0.917 and 0.993, leave-one-out cross validated Q2cm of 0.835, 0.865 and 0.899, and root-mean-square error for estimated error （RMSEE） of 0.396, 0.187and 0.22, respectively. Satisfactory results showed that, as new amino acid scales, data of HSEHPCSV may be a useful structural expression methodology＇for the studies on peptide QSAR （quantitative structure-activity relationship） due to many advantages such as plentiful structural information, definite physical and chemical meaning and easy interpretation.展开更多
The antioxidant and gap junctional communication（GJC） activities of carotenoids are known to be the two main anticancer mechanisms.Quantitative structure-activity relationship（QSAR） models of the two activities we...The antioxidant and gap junctional communication（GJC） activities of carotenoids are known to be the two main anticancer mechanisms.Quantitative structure-activity relationship（QSAR） models of the two activities were developed using stepwise regression and multilayer perceptron neural network based on the calculated descriptors of quantum chemistry.The results showed that the significant molecular descriptor related to the antioxidant activity of carotenoids was the HOMO-LUMO energy gap（EHL） and the molecular descriptor related to the GJC was the lowest unoccupied molecular orbital energy（ELUMO）.The two models of antioxidant activity both showed good predictive power,but the predictive power of the neural network QSAR model of antioxidant activity was better.In addition,the two GJC models have similar,moderate predictive power.The possible mechanisms of antioxidant activity and GJC of carotenoids were discussed.展开更多
In this study, solutions of hydrazine and its derivatives were irradiated using a pulsed electron beam to determine the half-reaction time of radiolysis. 3 D structures of the hydrazine derivatives were optimized, and...In this study, solutions of hydrazine and its derivatives were irradiated using a pulsed electron beam to determine the half-reaction time of radiolysis. 3 D structures of the hydrazine derivatives were optimized, and their energies were calculated using density functional theory with the B3 LYP method and 6-311 +(3 d, 3 p) basis set.For the first time, the 3 D quantitative structure-activity relationship(QSAR) equation describing the relationship between the hydrazine derivative structures and rate of radiolysis has been established using SPSS software.Pearson correlation analysis revealed a close correlation between the total energies of the molecules and half-reaction times. In the QSAR equation, Y =-7583.464 +54.687 X_1+94333.586 X_2,Y,X_1,and X_2 are the half-reaction time, total energy of the molecule, and orbital transition energy, respectively. The significance levels of the regression coefficients were 0.006 and 0.031, i.e., both less than 0.05. Thus, this model fully explains the relationship between hydrazine derivatives and β radiolysis stability.The results show that the total energy of the molecule and orbital transition energy are the main factors that influence the β radiolysis stability of these hydrazine derivatives.展开更多
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
The reactivity parameters,Q and e,in the Q-e scheme reflect the reactivities of a monomer(or a radical)in free-radical copolymerizations.By applying multiple linear regression(MLR)analysis,the optimal quantitative str...The reactivity parameters,Q and e,in the Q-e scheme reflect the reactivities of a monomer(or a radical)in free-radical copolymerizations.By applying multiple linear regression(MLR)analysis,the optimal quantitative structure-activity relationship(QSAR)model for the reactivity parameter lnQ was developed based on five descriptors(NAF,NOF,EαLUMO,EβHOMO,and EβLUMO)and 69 monomers with the root mean square(rms)error of 0.61.The optimal MLR model of the parameter e obtained from five descriptors(TOcl,NpN,NSO,EαHOMO and DH)and 68 monomers produced rms error of 0.42.Compared with previous models,the two optimal MLR models in this paper show satisfactory statistical characteristics.The feasibility of combining 2D descriptors obtained from the monomers and 3D descriptors calculated from the radical structures(formed from monomers+H )to predict parameters Q and e has been demonstrated.展开更多
The structure-activity relationship of several drugs with similar structure has been investigated by using ab initio method. The relation between the dipole moments and biological activities of these drugs was judged ...The structure-activity relationship of several drugs with similar structure has been investigated by using ab initio method. The relation between the dipole moments and biological activities of these drugs was judged after comparing their geometric structures, dipole moments and inhibitory concentrations. In principle, new drug molecule could be reasonably designed by altering the place of groups and ultimately, the potential drug could be screened by comparing the dipole moments of obtained molecules.展开更多
A molecular electronegativity distance vector(M)based on 13 atomic types has been used to describe the structures of 19 conjugates(LHCc)of levofloxacin-thiadiazole HDAC inhibitor(HDACi)and related inhibitory activitie...A molecular electronegativity distance vector(M)based on 13 atomic types has been used to describe the structures of 19 conjugates(LHCc)of levofloxacin-thiadiazole HDAC inhibitor(HDACi)and related inhibitory activities(pH,i=1,2,6)of LHCc against histone deacetylases(HDACs,such as HDAC1,HDAC2 and HDAC6).The quantitative structure-activity relationships(QSAR)were established by using leaps-and-bounds regression analysis for the inhibitory activities(pH)of 19 above compounds to HDAC1,HDAC2 and HDAC6 along with M.The correlation coefficients(R~2)and the leave-one-out(LOO)cross validation Rfor the pH,pHand pHmodels were 0.976 and 0.949;0.985 and 0.977;0.976 and 0.932,respectively.The QSAR models had favorable correlations,as well as robustness and good prediction capability by R~2,F,R~2,A,Fand Vtests.Validated by using 3876 training sets,the models have good external prediction ability.The results indicate that the molecular structural units:–CH–(g=1,2),–NH,–OH,=O,–O–and–S–are the main factors which can affect the inhibitory activity of pH,pHas well as pHbioactivities of these compounds directly.Accordingly,the main interactions between HDACs inhibitor and HDACs are hydrophobic interaction,hydrogen bond,and coordination with Znto form compounds,which is consistent with the results in reports.展开更多
藻类是水生食物网中主要的初级生产者,对水生生态系统的可持续性起着重要作用。随着社会发展、工业进步和人类活动,大量化学品被释放到水生环境中,对藻类产生了极大的威胁。若藻类受到危害势必会影响其他水生生物,因此有必要开展藻类的...藻类是水生食物网中主要的初级生产者,对水生生态系统的可持续性起着重要作用。随着社会发展、工业进步和人类活动,大量化学品被释放到水生环境中,对藻类产生了极大的威胁。若藻类受到危害势必会影响其他水生生物,因此有必要开展藻类的毒性评估。藻类的毒性评估需要大量的毒性数据,通过实验的方法获得水生毒性数据成本较高且比较耗时,定量构效关系(QSAR)是解决这类问题的一种良好的替代方法。本研究基于Web of Science与中国知网数据库文献中的53条急性毒性数据,利用极限梯度提升(XGB)算法和特征筛选方法建立了羊角月牙藻(Selenastrum capricornutum)急性毒性的QSAR模型。最优模型的训练集决定系数(R^(2)_(TR))达到了0.97,验证集决定系数(Q^(2)_(EXT))达到了0.78,留一法交叉验证系数(Q^(2)_(LOO))也达到了0.51,表明建立的QSAR模型具有较好的拟合优度、稳健性和预测能力。机理解释结果表明,化合物的拓扑电荷数、总原子序数和电负性是影响羊角月牙藻急性毒性的关键因素。在此基础上,采用建立的QSAR模型和EPI Suite分别预测了16种典型多环芳烃(PAHs)对藻类的急性毒性,并对其进行了毒性分级。研究结果为藻类的急性毒性数据的获取提供了一个高效预测工具,有利于加快化学品的水环境风险评估工作。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 relationship between chemical structures and photodegradation activity of 12 PAHs is studied using DFT and HF methods, and stepwise multiple linear regression analysis method. The equilibrium geometries and vibrat...The relationship between chemical structures and photodegradation activity of 12 PAHs is studied using DFT and HF methods, and stepwise multiple linear regression analysis method. The equilibrium geometries and vibration frequency have been investigated by considering Solvent effects using a selfconsistent reaction field based on the polarizable continuum model. With DFT and HF methods, different quantum chemical structural descriptors are obtained by quantum chemical calculation and the results with DFT method are better for QSAR model. It is concluded that the photodegradation activity is closely related to its molecular structure. In the regression analysis, the main factors affecting photodegradation rate include the energy of the highest occupied orbital EHOMO and the number of six-carbon benzene ring N1, and the QSAR model successfully established is logkb = 6.046 + 54.830EHOMO + 0.272N1. Statistical evaluation of the developed QSAR shows that the relationships are statistically significant and the model has good predictive ability. EHOMO is the most important factor influcing the photodegradation of PAHs, because the higher EHOMO is, the more easily electron will be excited and the more easily molecular will be degraded. Comparison of the photodegradation of PAHs with their biodegradation shows that the committed step of biodegradation is that the effects of microorganisms make the chemical bond break, while in the committed step of photodegradation PAHs eject electrons.展开更多
基金supported by the Natural Science Foundation of Fujian Province (D0710019)the Natural Science Foundation of Overseas Chinese Affairs Office of the State Council (06QZR09)
文摘With the artificial neural network（ANN） method combined with the multiple linear regression（MLR）,based on a series of quantum chemical descriptors and molecular connectivity indexes,quantitative structure-activity relationship（QSAR） models to predict the acute toxicity（-lgEC50） of substituted aromatic compounds to Photobacterium phosphoreum were established.Four molecular descriptors that appear in the MLR model,namely,the second order valence molecular connectivity index（2XV）,the energy of the highest occupied molecular orbital（EHOMO）,the logarithm of n-octyl alcohol/water partition coefficient（logKow） and the Connolly molecular area（MA）,were inputs of the ANN model.The root-mean-square error（RMSE） of the training and validation sets of the ANN model are 0.1359 and 0.2523,and the correlation coefficient（R） is 0.9810 and 0.8681,respectively.The leave-one-out（LOO） cross validated correlation coefficient（Q L2OO） of the MLR and ANN models is 0.6954 and 0.6708,respectively.The result showed that the two methods are complementary in the calculations.The regression method gave support to the neural network with physical explanation,and the neural network method gave a more accurate model for QSAR.In addition,some insights into the structural factors affecting the acute toxicity and toxicity mechanism of substituted aromatic compounds were discussed.
文摘The pathogenesis of Alzheimer’s disease (AD) putatively involves a compromised blood-brain barrier (BBB). In particular, the importance of brain-to-blood transport of brain-derived metabolites across the BBB has gained increasing attention as a potential mechanism in the pathogenesis of neurodegenerative disorders such as AD, which is characterized by the aberrant polymerization and accumulation of specific misfolded proteins, particularly β-amyloid (Aβ), a neuropathological hallmark of AD. P-glycoprotein (P-gp), a major component of the BBB, plays a role in the etiology of AD through Aβ clearance from the brain. Our QSAR models on a series of purine-type and propafenone-type substrates of P-gp showed that the interaction between P-gp and its modulators depended on Molar Refractivity, LogP, and Shape Attribute of drugs it transports. Meanwhile, another model on BBB partitioning of some compounds revealed that BBB partitioning relied upon the polar surface area, LogP, Balaban Index, the strength of a molecule combined with the membrane-water complex, and the changeability of the structure of a solute-membrane-water complex. The predictive model on BBB partitioning contributes to the discovery of some molecules through BBB as potential AD therapeutic drugs. Moreover, the interaction model of P-gp and modulators for treatment of multidrug resistance (MDR) indicates the discovery of some molecules to increase Aβ clearance from the brain and reduce Aβ brain accumulation by regulating BBB P-gp in the early stages of AD. The mechanism provides a new insight into the therapeutic strategy for AD.
基金Project supported by the Natural Science Foundation of Shanghai, China(No. 06ZR14002).
文摘Quantitative structure-biodegradability relationships （QSBRs） were established to develop predictive models and mechanistic explanations for acid dyestuffs as well as biological activities. With a total of four descriptors, molecular weight （MW）, energies of the highest occupied molecular orbital （EHOMO）, the lowest unoccupied molecular orbital （ELUMO）, and the excited state （EES）, calculated using quantum chemical semi-empirical methodology, a series of models were analyzed between the dye biodegradability and each descriptor. Results showed that EHOMO and Mw were the dominant parameters controlling the biodegradability of acid dyes. A statistically robust QSBR model was developed for all studied dyes, with the combined application of EHOMO and Mw. The calculated biodegradations fitted well with the experimental data monitored in a facultative-aerobic process, indicative of the reliable prediction and mechanistic character of the developed model.
文摘The genotoxicity of 22 substituted nitrobenzenes were evaluated by the chromosome aberrations test in in vitro human peripheral lymphocytes.18 of 22 compounds exhibit genotoxic activities.Quantitative structure-activity relationship model was established to correlate the genotoxicity of substituted nitrobenzenes with the characteristics of the substituents on benzene ring.
基金Supported by the Chinese National Key Technologies R & D Program of 11th Five-year Plan (2006BAD27B06)Education Foundation of Innovative Engineering Key Project of Education Department (707034)
文摘Carotenoids are a family of effective active oxygen scavengers, which can reduce the danger of occurrence of chronic diseases such as cardiovascular disease, cataract, cancer, and so on. The quantitative structure-activity relationship （QSAR） equation between carotenoids and antioxidant activity was established by quantum chemistry AM1, molecular mechanism （MM＋） and stepwise regression analysis methods, and the model was evaluated by leave-one-out approach. The results showed that the significant molecular descriptors related to the antioxidant activity of carotenoids were the energy difference （E_HL） between the lowest unoccupied molecular orbital （LUMO） and the highest occupied molecular orbital （HOMO） and ionization energy （Eiso）. The model showed a good predictive ability （Q^2 〉 0.5）.
基金Supported by the National High Technology Research and Development Program of China (863 Program, No. 2006AA02Z312)
文摘A new set of descriptors, HSEHPCSV （component score vector of hydrophobic, steric, and electronic properties together with hydrogen bonding contributions）, were derived from principal component analyses of 95 physicochemical variables of 20 natural amino acids separately according to different kinds of properties described, namely, hydrophobic, steric, and electronic properties as well as hydrogen bonding contributions. HSEHPCSV scales were then employed to express structures of angiotensin-converting enzyme inhibitors, bitter tasting thresholds and bactericidal 18 peptide, and to construct QSAR models based on partial least square （PLS）. The results obtained are as follows： the multiple correlation coefficient （R2cum） of 0.846, 0.917 and 0.993, leave-one-out cross validated Q2cm of 0.835, 0.865 and 0.899, and root-mean-square error for estimated error （RMSEE） of 0.396, 0.187and 0.22, respectively. Satisfactory results showed that, as new amino acid scales, data of HSEHPCSV may be a useful structural expression methodology＇for the studies on peptide QSAR （quantitative structure-activity relationship） due to many advantages such as plentiful structural information, definite physical and chemical meaning and easy interpretation.
基金Supported by the Chinese National Key Technologies R&D Program of 11th Five-year Plan (2006BAD27B06)the Fundamental Research Funds for the Central Universities and Education Foundation of Innovative Engineering Key Project of Education Department (707034)
文摘The antioxidant and gap junctional communication（GJC） activities of carotenoids are known to be the two main anticancer mechanisms.Quantitative structure-activity relationship（QSAR） models of the two activities were developed using stepwise regression and multilayer perceptron neural network based on the calculated descriptors of quantum chemistry.The results showed that the significant molecular descriptor related to the antioxidant activity of carotenoids was the HOMO-LUMO energy gap（EHL） and the molecular descriptor related to the GJC was the lowest unoccupied molecular orbital energy（ELUMO）.The two models of antioxidant activity both showed good predictive power,but the predictive power of the neural network QSAR model of antioxidant activity was better.In addition,the two GJC models have similar,moderate predictive power.The possible mechanisms of antioxidant activity and GJC of carotenoids were discussed.
文摘In this study, solutions of hydrazine and its derivatives were irradiated using a pulsed electron beam to determine the half-reaction time of radiolysis. 3 D structures of the hydrazine derivatives were optimized, and their energies were calculated using density functional theory with the B3 LYP method and 6-311 +(3 d, 3 p) basis set.For the first time, the 3 D quantitative structure-activity relationship(QSAR) equation describing the relationship between the hydrazine derivative structures and rate of radiolysis has been established using SPSS software.Pearson correlation analysis revealed a close correlation between the total energies of the molecules and half-reaction times. In the QSAR equation, Y =-7583.464 +54.687 X_1+94333.586 X_2,Y,X_1,and X_2 are the half-reaction time, total energy of the molecule, and orbital transition energy, respectively. The significance levels of the regression coefficients were 0.006 and 0.031, i.e., both less than 0.05. Thus, this model fully explains the relationship between hydrazine derivatives and β radiolysis stability.The results show that the total energy of the molecule and orbital transition energy are the main factors that influence the β radiolysis stability of these hydrazine derivatives.
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supported by the National Natural Science Foundation of China(No.21472040)the Scientific Research Fund of Hunan Education Department(Nos.16A047 and 18A344)the Open Project Program of Hunan Provincial Key Laboratory of Environmental Catalysis & Waste Regeneration(Hunan Institute of Engineering)(2018KF11)
文摘The reactivity parameters,Q and e,in the Q-e scheme reflect the reactivities of a monomer(or a radical)in free-radical copolymerizations.By applying multiple linear regression(MLR)analysis,the optimal quantitative structure-activity relationship(QSAR)model for the reactivity parameter lnQ was developed based on five descriptors(NAF,NOF,EαLUMO,EβHOMO,and EβLUMO)and 69 monomers with the root mean square(rms)error of 0.61.The optimal MLR model of the parameter e obtained from five descriptors(TOcl,NpN,NSO,EαHOMO and DH)and 68 monomers produced rms error of 0.42.Compared with previous models,the two optimal MLR models in this paper show satisfactory statistical characteristics.The feasibility of combining 2D descriptors obtained from the monomers and 3D descriptors calculated from the radical structures(formed from monomers+H )to predict parameters Q and e has been demonstrated.
基金The project was supported by the National Natural Science Foundation of China (No.10274055) and Natural Science Foundation of Henan Province (2004601107)
文摘The structure-activity relationship of several drugs with similar structure has been investigated by using ab initio method. The relation between the dipole moments and biological activities of these drugs was judged after comparing their geometric structures, dipole moments and inhibitory concentrations. In principle, new drug molecule could be reasonably designed by altering the place of groups and ultimately, the potential drug could be screened by comparing the dipole moments of obtained molecules.
基金supported by the National Natural Science Foundation of China(21473081,21075138)special fund of State Key Laboratory of Structure Chemistry(20160028)
文摘A molecular electronegativity distance vector(M)based on 13 atomic types has been used to describe the structures of 19 conjugates(LHCc)of levofloxacin-thiadiazole HDAC inhibitor(HDACi)and related inhibitory activities(pH,i=1,2,6)of LHCc against histone deacetylases(HDACs,such as HDAC1,HDAC2 and HDAC6).The quantitative structure-activity relationships(QSAR)were established by using leaps-and-bounds regression analysis for the inhibitory activities(pH)of 19 above compounds to HDAC1,HDAC2 and HDAC6 along with M.The correlation coefficients(R~2)and the leave-one-out(LOO)cross validation Rfor the pH,pHand pHmodels were 0.976 and 0.949;0.985 and 0.977;0.976 and 0.932,respectively.The QSAR models had favorable correlations,as well as robustness and good prediction capability by R~2,F,R~2,A,Fand Vtests.Validated by using 3876 training sets,the models have good external prediction ability.The results indicate that the molecular structural units:–CH–(g=1,2),–NH,–OH,=O,–O–and–S–are the main factors which can affect the inhibitory activity of pH,pHas well as pHbioactivities of these compounds directly.Accordingly,the main interactions between HDACs inhibitor and HDACs are hydrophobic interaction,hydrogen bond,and coordination with Znto form compounds,which is consistent with the results in reports.
文摘藻类是水生食物网中主要的初级生产者,对水生生态系统的可持续性起着重要作用。随着社会发展、工业进步和人类活动,大量化学品被释放到水生环境中,对藻类产生了极大的威胁。若藻类受到危害势必会影响其他水生生物,因此有必要开展藻类的毒性评估。藻类的毒性评估需要大量的毒性数据,通过实验的方法获得水生毒性数据成本较高且比较耗时,定量构效关系(QSAR)是解决这类问题的一种良好的替代方法。本研究基于Web of Science与中国知网数据库文献中的53条急性毒性数据,利用极限梯度提升(XGB)算法和特征筛选方法建立了羊角月牙藻(Selenastrum capricornutum)急性毒性的QSAR模型。最优模型的训练集决定系数(R^(2)_(TR))达到了0.97,验证集决定系数(Q^(2)_(EXT))达到了0.78,留一法交叉验证系数(Q^(2)_(LOO))也达到了0.51,表明建立的QSAR模型具有较好的拟合优度、稳健性和预测能力。机理解释结果表明,化合物的拓扑电荷数、总原子序数和电负性是影响羊角月牙藻急性毒性的关键因素。在此基础上,采用建立的QSAR模型和EPI Suite分别预测了16种典型多环芳烃(PAHs)对藻类的急性毒性,并对其进行了毒性分级。研究结果为藻类的急性毒性数据的获取提供了一个高效预测工具,有利于加快化学品的水环境风险评估工作。
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 Natural Science Foundation of China(Nos.40976041 and 20775074)
文摘The relationship between chemical structures and photodegradation activity of 12 PAHs is studied using DFT and HF methods, and stepwise multiple linear regression analysis method. The equilibrium geometries and vibration frequency have been investigated by considering Solvent effects using a selfconsistent reaction field based on the polarizable continuum model. With DFT and HF methods, different quantum chemical structural descriptors are obtained by quantum chemical calculation and the results with DFT method are better for QSAR model. It is concluded that the photodegradation activity is closely related to its molecular structure. In the regression analysis, the main factors affecting photodegradation rate include the energy of the highest occupied orbital EHOMO and the number of six-carbon benzene ring N1, and the QSAR model successfully established is logkb = 6.046 + 54.830EHOMO + 0.272N1. Statistical evaluation of the developed QSAR shows that the relationships are statistically significant and the model has good predictive ability. EHOMO is the most important factor influcing the photodegradation of PAHs, because the higher EHOMO is, the more easily electron will be excited and the more easily molecular will be degraded. Comparison of the photodegradation of PAHs with their biodegradation shows that the committed step of biodegradation is that the effects of microorganisms make the chemical bond break, while in the committed step of photodegradation PAHs eject electrons.
