Development and validation of a genetic algorithm for flexible docking
Development and validation of a genetic algorithm for flexible docking
复制标题
DOI：
10.1006/jmbi.1996.0897
复制
发表时间：
1997-04-04
影响因子：
5.6
通讯作者：
Taylor, R
中科院分区：
文献类型：
--
作者：
Jones, G;Willett, P;Taylor, R
在合理药物设计中（“对接”问题），预测小分子与已知三维结构的大分子的结合模式是一个至关重要的问题。我们报道了GOLD（配体对接的遗传优化）程序的开发和验证。GOLD是一种自动配体对接程序，它使用遗传算法来探索配体的全方位构象灵活性以及蛋白质的部分灵活性，并满足配体在结合时必须置换松散结合的水这一基本要求。对原始技术进行了大量的改进和修正，使得该算法的可靠性和适用性大幅提高。这种先进的算法已经在从布鲁克海文蛋白质数据库中提取的100个复合物数据集上进行了测试。当用于将配体重新对接到结合位点时，GOLD在确定实验结合模式方面达到了71%的成功率。（C）1997年学术出版社有限公司。
Prediction of small molecule binding modes to macromolecules of known three-dimensional structure is a problem of paramount importance in rational drug design (the ''docking'' problem). We report the development and validation of the program GOLD (Genetic Optimisation for Ligand Docking). GOLD is an automated Ligand docking program that uses a genetic algorithm to explore the full range of ligand conformational flexibility with partial flexibility of the protein, and satisfies the fundamental requirement that the ligand must displace loosely bound water on binding. Numerous enhancements and modifications have been applied to the original technique resulting in a substantial increase in the reliability and the applicability of the algorithm. The advanced algorithm has been tested on a dataset of 100 complexes extracted from the Brookhaven Protein DataBank. When used to dock the ligand back into the binding site, GOLD achieved a 71% success rate in identifying the experimental binding mode. (C) 1997 Academic Press Limited.