Ligand-based prediction of active conformation by 3D-QSAR flexibility descriptors and their application in 3+3D-QSAR models
Ligand-based prediction of active conformation by 3D-QSAR flexibility descriptors and their application in 3+3D-QSAR models
复制标题
DOI：
10.1021/jm049157i
复制
发表时间：
2005-05-05
影响因子：
7.3
通讯作者：
Fülöp, F
中科院分区：
文献类型：
--
作者：
Martinek, TA;Ötvös, F;Fülöp, F
一个概念上新的3D分子描述符的类型和方法推导出简单的统计热力学推理，基于自由能的变化过程中遇到的一个构象合奏的配体的活性构象的转变。首先在37个具有μ-阿片活性的内吗啡肽类似物上测试描述符的性能。该方法导致预测的3D-QSAR模型，并预测活性构象。该方法可以与传统的3D-QSAR技术以3+3D-QSAR的方式相结合。在一系列具有抗氧化活性的38种PGF 2 α前列腺素类似物上测试了这一特征;估计了分子灵活性解释生物活性变化的程度，并预测了活性构象。新的描述符与基于网格的SOMFA描述符相结合，导致3+3D-QSAR模型具有良好的预测水平，导致分离的活性构象的分子相互作用场的影响和构象自由能损失的影响的方法。
A conceptionally new 3D molecular descriptor type and methodology are deduced by simple statistical thermodynamic reasoning, based on the free energy change encountered during a transformation of a conformational ensemble of the ligand to an active conformation. The performance of the descriptor was first tested on 37 endomorphin analogues with μ-opiate activity. The method resulted in predictive 3D-QSAR models, and the active conformation was also predicted. Generally, the methodology can be combined with the traditional 3D-QSAR techniques in a 3+3D-QSAR manner. This feature was tested on a series of 38 PGF2α prostaglandin analogues with antinidatory activity; the extent to which the molecular flexibility explains the variation in the biological activity was estimated and the active conformation was predicted. The novel descriptors in combination with the grid-based SOMFA descriptors resulted in 3+3D-QSAR models with good levels of predictivity leading to the approach of separation of the effect of the molecular interaction field of the active conformation and the effect of the conformational free energy loss.