Kızılcan Dilek Şeyma, Güzel Yahya, Türkmenoğlu Burçin
Department of Chemistry, Faculty of Science, Erciyes University, Kayseri, Turkey.
Department of Analytical Chemistry, Faculty of Pharmacy, Erzincan Binali Yıldırım University, Erzincan, Turkey.
Mol Divers. 2024 Dec;28(6):4087-4104. doi: 10.1007/s11030-023-10798-1. Epub 2024 Jan 28.
The behavior of a molecule within its environment is governed by chemical fields present in 3D space. However, beyond local descriptors in 3D, the conformations a molecule assumes, and the resulting clusters also play a role in influencing structure-activity models. This study focuses on the clustering of atoms according to the vector space of four atoms aligned in the Z-Matrix Reference system for molecular similarity. Using 3D-QSAR analysis, it was aimed to determine the pharmacophore groups as interaction points in the binding region of the β2-adrenoceptor target of fenoterol stereoisomers. Different types of local reactive descriptors of ligands have been used to elucidate points of interaction with the target. Activity values for ligand-receptor interaction energy were determined using the Levenberg-Marquardt algorithm. Using the Molecular Comparative Electron Topology method, the 3D pharmacophore model (3D-PhaM) was obtained after aligning and superimposing the molecules and was further validated by the molecular docking method. Best guesses were calculated with a non-output validation (LOO-CV) method. Finally, the data were calculated using the 'graphic fingerprint' technique. Based on the eLKlopman (Electrostatic LUMO Klopman) descriptor, the Q value of this derivative set was calculated as 0.981 and the R value is calculated as 0.998.
分子在其环境中的行为受三维空间中存在的化学场支配。然而，除了三维空间中的局部描述符外，分子所呈现的构象以及由此产生的簇在影响结构-活性模型方面也发挥着作用。本研究着重于根据在分子相似性的Z矩阵参考系统中排列的四个原子的向量空间对原子进行聚类。使用三维定量构效关系（3D-QSAR）分析，旨在确定作为非诺特罗立体异构体β2-肾上腺素能受体靶点结合区域中相互作用点的药效基团。已使用不同类型的配体局部反应性描述符来阐明与靶点的相互作用点。使用Levenberg-Marquardt算法确定配体-受体相互作用能的活性值。使用分子比较电子拓扑方法，在对分子进行排列和叠加后获得三维药效团模型（3D-PhaM），并通过分子对接方法进一步验证。使用非输出验证（留一法交叉验证，LOO-CV）方法计算最佳猜测值。最后，使用“图形指纹”技术计算数据。基于电子LUMO Klopman（eLKlopman）描述符，该衍生物集的Q值计算为0.981，R值计算为0.998。
