Devinyak Oleg, Havrylyuk Dmytro, Lesyk Roman
Department of Pharmaceutical Disciplines, Uzhgorod National University, 88000 Uzhgorod, Ukraine.
Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, 79010 Lviv, Ukraine.
J Mol Graph Model. 2014 Nov;54:194-203. doi: 10.1016/j.jmgm.2014.10.006. Epub 2014 Nov 4.
3D-MoRSE is a very flexible 3D structure encoding framework for chemoinformatics and QSAR purposes due to the range of scattering parameter values and variety of weighting schemes used. While arising in many QSAR studies, up to this time they were considered as hardly interpreted and were treated like a "black box". This study is intended to lift the veil of mystery, providing a comprehensible way to the interpretation of 3D-MoRSE descriptors in QSAR/QSPR studies. The values of these descriptors are calculated with rather simple equation, but may vary when using differing starting geometries as optimization input. This variation increases with scattering parameter and also is higher for electronegativity weighted and unweighted descriptors. Though each 3D-MoRSE descriptor incorporates the information about the whole molecule structure, its final value is derived mostly from short-distance (up to 3Å) atomic pairs. And, if a QSAR study covers structurally similar set of compounds, then the role of 3D-MoRSE descriptor in a model can be interpreted using just several pairs of neighbor atoms. The guide to interpretation process is discussed and illustrated with a case study. Realizing the mathematical concept behind 3D-descriptors and knowing their properties it is easy not only to interpret, but also to predict the importance of 3D-MoRSE descriptors in a QSAR study. The process of prediction is described on the practical example and its accuracy is confirmed with further QSAR modeling.
由于散射参数值的范围和所使用的加权方案的多样性，3D - MoRSE是一种用于化学信息学和定量构效关系（QSAR）目的的非常灵活的三维结构编码框架。虽然在许多QSAR研究中都会出现，但直到现在，它们都被认为难以解释，并且被当作“黑匣子”来对待。本研究旨在揭开其神秘面纱，为在QSAR / QSPR研究中解释3D - MoRSE描述符提供一种可理解的方法。这些描述符的值是通过相当简单的方程式计算得出的，但在使用不同的起始几何结构作为优化输入时可能会有所不同。这种变化随着散射参数的增加而增大，并且对于电负性加权和未加权的描述符来说也更高。尽管每个3D - MoRSE描述符都包含了关于整个分子结构的信息，但其最终值主要来自短距离（至多3Å）的原子对。而且，如果一个QSAR研究涵盖了结构相似的一组化合物，那么在一个模型中3D - MoRSE描述符的作用可以仅通过几对相邻原子来解释。本文通过一个案例研究讨论并说明了解释过程。了解3D描述符背后的数学概念并知晓它们的性质，就不仅易于解释，而且能够预测3D - MoRSE描述符在QSAR研究中的重要性。预测过程在实际例子中进行了描述，并且通过进一步的QSAR建模证实了其准确性。
