Atanasova Mariyana, Yordanov Nikola, Dimitrov Ivan, Berkov Strahil, Doytchinova Irini
Medical University of Sofia, Faculty of Pharmacy, 2 Dunav st., 1000 Sofia, Bulgaria tel: +359 2 9236506.
Institute of Biodiversity and Ecosystem Research, 23 Acad. G Bonchev str, 1113 Sofia, Bulgaria.
Mol Inform. 2015 Jun;34(6-7):394-403. doi: 10.1002/minf.201400145. Epub 2015 Jun 19.
A training set of 22 synthetic galantamine derivatives binding to acetylcholinesterase was docked by GOLD and the protocol was optimized in terms of scoring function, rigidity/flexibility of the binding site, presence/absence of a water molecule inside and radius of the binding site. A moderate correlation was found between the affinities of compounds expressed as pIC50 values and their docking scores. The optimized docking protocol was validated by an external test set of 11 natural galantamine derivatives and the correlation coefficient between the docking scores and the pIC50 values was 0.800. The derived relationship was used to analyze the interactions between galantamine derivatives and AChE.
通过GOLD对接了22种与乙酰胆碱酯酶结合的合成加兰他敏衍生物的训练集，并在评分函数、结合位点的刚性/柔性、结合位点内部水分子的存在与否以及结合位点半径方面对方案进行了优化。发现以pIC50值表示的化合物亲和力与其对接分数之间存在适度的相关性。通过11种天然加兰他敏衍生物的外部测试集对优化后的对接方案进行了验证，对接分数与pIC50值之间的相关系数为0.800。利用得出的关系分析了加兰他敏衍生物与乙酰胆碱酯酶之间的相互作用。
