In this study. an automated conformer selection procedure using generic algorithm (GA) has been applied in comparative molecular field analysis (CoMFA) method. Using genetic algorithm. the 3D-QSAR model is optimized t...In this study. an automated conformer selection procedure using generic algorithm (GA) has been applied in comparative molecular field analysis (CoMFA) method. Using genetic algorithm. the 3D-QSAR model is optimized to an optimal one. From the calculation results, a group of QSAR models with high predictive ability can be obtained, which is superior than using conventional CoMFA: meanwhile. the active conformers for these compounds in data set can be determined fi om the best model.展开更多
In terms of formation mechanisms of linear dunes,there are open arguments for their widespread distribution and multi-morphological diversities.In order to clarify the formation mechanism of linear dunes of Qarhan Sal...In terms of formation mechanisms of linear dunes,there are open arguments for their widespread distribution and multi-morphological diversities.In order to clarify the formation mechanism of linear dunes of Qarhan Salt Lake,we used pattern analysis method to analyze the statistical characteristics and spatial variation of their pattern parameters.Except at the west-northwest margin,the pattern parameters showed regular spatial variation from the up-middle part towards the downwind end of the dune field.Based on the cumulative probability plots for inter-crest spacing and crest length,we divided the linear dunes into three groups,which corresponding to the three evolution stages of these dunes.The first group comprises erosional relics,with shorter crests,smaller inter-crest spacing and more random dune orientation.The second group comprises dunes whose sand supply is just sufficient to maintain stability and these dunes are approaching the net erosion stage.The crest length and inter-crest spacing of these dunes are much larger than those of the first group,and dune orientation is closer to the resultant drift direction （RDD） .The last group comprises linear dunes that are still undergoing vertical accretion and longitudinal elongation,which follows the RDD of the modern wind regime.The presence of regular spatial variation of pattern parameters and a similar geometry with the vegetated linear dunes suggest that deposition and erosion coexist in the development and evolution of linear dunes of Qarhan Salt Lake,i.e.deposition predominates at the downwind end of linear dunes in the vertical accretion and longitudinal elongation stage,whereas erosion mainly occurs at the upwind end of linear dunes in the degradation stage.Therefore,the formation mechanism of linear dunes in Qarhan Salt Lake can be reasonably explained by the combination of depositional and erosional theories.展开更多
Three-dimensional quantitative structure activity relationship （3D-QSAR） and docking studies of a series of arylthioindole derivatives as tubulin inhibitors against human breast cancer cell line MCF-7 have been carr...Three-dimensional quantitative structure activity relationship （3D-QSAR） and docking studies of a series of arylthioindole derivatives as tubulin inhibitors against human breast cancer cell line MCF-7 have been carried out. An optimal 3D-QSAR model from the comparative molecular field analysis （CoMFA） for training set with significant statistical quality （R2=0.898） and predictive ability （q2=0.654） was established. The same model was further applied to predict pIC50 values of the compounds in test set, and the resulting predictive correlation coefficient R2（pred） reaches 0.816, further showing that this CoMFA model has high predictive ability. Moreover, the appropriate binding orientations and conformations of these compounds interacting with tubulin are located by docking study, and it is very interesting to find the consistency between the CoMFA field distribution and the 3D topology structure of active site of tubulin. Based on CoMFA along with docking results, some important factors improving the activities of these compounds were discussed in detail and were summarized as follows： the substituents R3-R5 （on the phenyl ring） with higher electronegativity, the substituent R6 with higher eleetropositivity and bigger bulk, the substituent R7 with smaller bulk, and so on. In addition, five new compounds with higher activities have been designed. Such results can offer useful theoretical references for experimental works.展开更多
Canceling grids accommodating probes in comparative molecular field analysis (CoMFA), the idea of flexibleness is introduced into the CoMFA, and in combination with swarm intelligent algorithm which attempts to optimi...Canceling grids accommodating probes in comparative molecular field analysis (CoMFA), the idea of flexibleness is introduced into the CoMFA, and in combination with swarm intelligent algorithm which attempts to optimize distributions of diverse probes around drug molecules, a new 3D-QSAR method is proposed in this context as flexible comparative molecular field analysis (FCoMFA). In preliminary at-tempts to performing QSAR studies on 47 glycogen phosphorylase inhibitors, FCoMFA is employed and confirmed to be potent to exploring ligand-receptor interaction manners at active positions and thus to generating stable and predictable models. Simultaneously by an intuitive graphics regarding probe distribution patterns, impacts of different substituted groups on activities is also given an insight into.展开更多
采用比较分子力场分析法(CoMFA)和比较分子相似性指数分析法(CoMSIA),对27个新型双酰基脲类化合物的杀蚊幼虫(Aedes aegypti L.)活性进行三维定量构效关系(3D-QSAR)研究.在CoMFA研究中,考察了网格点步长对统计结果的影响.在CoMSIA研究中...采用比较分子力场分析法(CoMFA)和比较分子相似性指数分析法(CoMSIA),对27个新型双酰基脲类化合物的杀蚊幼虫(Aedes aegypti L.)活性进行三维定量构效关系(3D-QSAR)研究.在CoMFA研究中,考察了网格点步长对统计结果的影响.在CoMSIA研究中,系统考察了各种分子场组合、网格点步长和衰减因子对模型统计结果的影响,发现立体场和氢键供体场的组合得到最佳模型.所建立的CoMFA和CoMSIA模型的非交叉验证相关系数r2值分别为0.828和0.841,并都具有较强的预测能力.CoMFA和CoMSIA模型的三维等值图不仅直观地解释了结构与活性的关系,而且为后续优化该系列化合物提供了理论依据.展开更多
文摘In this study. an automated conformer selection procedure using generic algorithm (GA) has been applied in comparative molecular field analysis (CoMFA) method. Using genetic algorithm. the 3D-QSAR model is optimized to an optimal one. From the calculation results, a group of QSAR models with high predictive ability can be obtained, which is superior than using conventional CoMFA: meanwhile. the active conformers for these compounds in data set can be determined fi om the best model.
基金funded by the National Basic Research Program of China (2013CB956000)the National Natural Science Foundation of China (41171010,41371102,41301003)
文摘In terms of formation mechanisms of linear dunes,there are open arguments for their widespread distribution and multi-morphological diversities.In order to clarify the formation mechanism of linear dunes of Qarhan Salt Lake,we used pattern analysis method to analyze the statistical characteristics and spatial variation of their pattern parameters.Except at the west-northwest margin,the pattern parameters showed regular spatial variation from the up-middle part towards the downwind end of the dune field.Based on the cumulative probability plots for inter-crest spacing and crest length,we divided the linear dunes into three groups,which corresponding to the three evolution stages of these dunes.The first group comprises erosional relics,with shorter crests,smaller inter-crest spacing and more random dune orientation.The second group comprises dunes whose sand supply is just sufficient to maintain stability and these dunes are approaching the net erosion stage.The crest length and inter-crest spacing of these dunes are much larger than those of the first group,and dune orientation is closer to the resultant drift direction （RDD） .The last group comprises linear dunes that are still undergoing vertical accretion and longitudinal elongation,which follows the RDD of the modern wind regime.The presence of regular spatial variation of pattern parameters and a similar geometry with the vegetated linear dunes suggest that deposition and erosion coexist in the development and evolution of linear dunes of Qarhan Salt Lake,i.e.deposition predominates at the downwind end of linear dunes in the vertical accretion and longitudinal elongation stage,whereas erosion mainly occurs at the upwind end of linear dunes in the degradation stage.Therefore,the formation mechanism of linear dunes in Qarhan Salt Lake can be reasonably explained by the combination of depositional and erosional theories.
基金This work was supported by the National Natural Science Foundation of China （No.20673148）. We heartily thank the Molecular Discovery Ltd. for giving us the Dock 6.0 program as a freeware and the College of Life Sciences, Sun Yat-Sen University for the SYBYL 6.9 computation environment support.
文摘Three-dimensional quantitative structure activity relationship （3D-QSAR） and docking studies of a series of arylthioindole derivatives as tubulin inhibitors against human breast cancer cell line MCF-7 have been carried out. An optimal 3D-QSAR model from the comparative molecular field analysis （CoMFA） for training set with significant statistical quality （R2=0.898） and predictive ability （q2=0.654） was established. The same model was further applied to predict pIC50 values of the compounds in test set, and the resulting predictive correlation coefficient R2（pred） reaches 0.816, further showing that this CoMFA model has high predictive ability. Moreover, the appropriate binding orientations and conformations of these compounds interacting with tubulin are located by docking study, and it is very interesting to find the consistency between the CoMFA field distribution and the 3D topology structure of active site of tubulin. Based on CoMFA along with docking results, some important factors improving the activities of these compounds were discussed in detail and were summarized as follows： the substituents R3-R5 （on the phenyl ring） with higher electronegativity, the substituent R6 with higher eleetropositivity and bigger bulk, the substituent R7 with smaller bulk, and so on. In addition, five new compounds with higher activities have been designed. Such results can offer useful theoretical references for experimental works.
基金Supported by National High Technology (863) Program (Grant No. 2006AA02Z312)the State Key Laboratory of Chemo/Biosensing and Chemometrics Foundation (Grant No. 0501201)Chongqing University Innovation Fund (Grant No. 030506)
文摘Canceling grids accommodating probes in comparative molecular field analysis (CoMFA), the idea of flexibleness is introduced into the CoMFA, and in combination with swarm intelligent algorithm which attempts to optimize distributions of diverse probes around drug molecules, a new 3D-QSAR method is proposed in this context as flexible comparative molecular field analysis (FCoMFA). In preliminary at-tempts to performing QSAR studies on 47 glycogen phosphorylase inhibitors, FCoMFA is employed and confirmed to be potent to exploring ligand-receptor interaction manners at active positions and thus to generating stable and predictable models. Simultaneously by an intuitive graphics regarding probe distribution patterns, impacts of different substituted groups on activities is also given an insight into.
文摘采用比较分子力场分析法(CoMFA)和比较分子相似性指数分析法(CoMSIA),对27个新型双酰基脲类化合物的杀蚊幼虫(Aedes aegypti L.)活性进行三维定量构效关系(3D-QSAR)研究.在CoMFA研究中,考察了网格点步长对统计结果的影响.在CoMSIA研究中,系统考察了各种分子场组合、网格点步长和衰减因子对模型统计结果的影响,发现立体场和氢键供体场的组合得到最佳模型.所建立的CoMFA和CoMSIA模型的非交叉验证相关系数r2值分别为0.828和0.841,并都具有较强的预测能力.CoMFA和CoMSIA模型的三维等值图不仅直观地解释了结构与活性的关系,而且为后续优化该系列化合物提供了理论依据.
