物理化学学报 >> 2005, Vol. 21 >> Issue (04): 372-377.doi: 10.3866/PKU.WHXB20050406

研究论文 上一篇    下一篇

基于遗传算法的Caco-2细胞穿透系数的研究

黄钦; 侯廷军; 徐筱杰   

  1. 北京大学化学与分子工程学院, 北京 100871
  • 收稿日期:2004-08-20 修回日期:2004-11-09 发布日期:2005-04-15
  • 通讯作者: 徐筱杰 E-mail:xiaojxu@pku.edu.cn

The Prediction of Caco-2 Permeation Based on Genetic Algorithm

HUANG Qin; HOU Ting -Jun; XU Xiao-Jie   

  1. College of Chemistry and Molecular Engineering, Peking University, Beijing 100871
  • Received:2004-08-20 Revised:2004-11-09 Published:2005-04-15
  • Contact: XU Xiao-Jie E-mail:xiaojxu@pku.edu.cn

摘要: 采用遗传算法研究了一系列药物分子的Caco-2细胞表观穿透系数(lgPeff)和分子结构之间的关系. 基于51个化合物构成的训练集, 计算得到了一组效果较好的定量构效关系(QSAR)模型. 这些模型不仅具有较好的回归能力, 还能对预测集中的分子进行较好的预测. 在计算得到的精华种群中, 共有4个分子参数具有较高的出现频率, 它们分别是lgD(表观酯水分配系数)、rgyr(回旋半径)、Shadow-Xlength(分子在X维上的投影长度)以及NHBD(氢键给体数目).

关键词: 药代动力学, 肠吸收, 定量构效关系, 遗传算法, Caco-2细胞

Abstract: In current work, the correlations between Caco-2 permeability(lgPeff) and molecular structures were investigated using genetic algorithm(GA). A group of multiple regression models with good statistical significance were obtained based on a training set of 51 molecules, from the statistical analyses of the descriptors used in the evolution procedure, four of them, including the distribution coefficient(lgD), radius of gyration(rgyr), shadow-X length(length of molecule in the X dimension), and NHBD, may have the largest impact on diffusion through Caco-2 cell.

Key words: Pharmacokinetics, Intestinal absorption, QSAR, Genetic algorithm, Caco-2