Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function
Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function
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DOI：
10.1002/(sici)1096-987x(19981115)19:14
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发表时间：
1998-11
影响因子：
3
通讯作者：
G. Morris;D. Goodsell;R. S. Halliday;R. Huey;W. Hart;R. Belew;A. Olson
中科院分区：
文献类型：
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作者：
G. Morris;D. Goodsell;R. S. Halliday;R. Huey;W. Hart;R. Belew;A. Olson
研究人员开发并测试了一种新型的、鲁棒的自动对接方法，该方法可以预测柔性配体与大分子靶标的结合构象，并结合了一个新的评分函数，该函数可以估计结合时的自由能变化。有趣的是，这种方法应用了拉马克的遗传学模型，其中个体表型的环境适应性被反向转录到其基因型中，并成为可遗传的特征。我们考虑了蒙特卡罗模拟退火、传统遗传算法和拉马克遗传算法三种搜索方法，并比较了它们在已知三维结构的7个蛋白质配体测试系统对接中的性能。研究表明，传统遗传算法和拉马克遗传算法都比早期AUTODOCK中使用的模拟退火方法具有更大的自由度，并且拉马克遗传算法是三种遗传算法中最有效、最可靠和最成功的。经验自由能函数使用一组30个结构已知的蛋白质配体配合物与实验确定的结合常数进行校准。根据各种结构衍生的分子性质对观察到的结合常数进行了线性回归分析。最终模型的残差标准误差为9.11 kJ mol−1 (2.177 kcal mol−1)，可作为新的能量函数。AUTODOCK 3.0版本提供了新的搜索方法和经验自由能函数。©1998 John Wiley & Sons, Inc[J] .计算机工程学报，2009,31 (2):559 - 567
A novel and robust automated docking method that predicts the bound conformations of flexible ligands to macromolecular targets has been developed and tested, in combination with a new scoring function that estimates the free energy change upon binding. Interestingly, this method applies a Lamarckian model of genetics, in which environmental adaptations of an individual's phenotype are reverse transcribed into its genotype and become heritable traits (sic). We consider three search methods, Monte Carlo simulated annealing, a traditional genetic algorithm, and the Lamarckian genetic algorithm, and compare their performance in dockings of seven protein–ligand test systems having known three‐dimensional structure. We show that both the traditional and Lamarckian genetic algorithms can handle ligands with more degrees of freedom than the simulated annealing method used in earlier versions of AUTODOCK, and that the Lamarckian genetic algorithm is the most efficient, reliable, and successful of the three. The empirical free energy function was calibrated using a set of 30 structurally known protein–ligand complexes with experimentally determined binding constants. Linear regression analysis of the observed binding constants in terms of a wide variety of structure‐derived molecular properties was performed. The final model had a residual standard error of 9.11 kJ mol−1 (2.177 kcal mol−1) and was chosen as the new energy function. The new search methods and empirical free energy function are available in AUTODOCK, version 3.0. © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 1639–1662, 1998