Department of Pharmaceutical Technology, JIS University, 81, Nilgunj Road, Agarpara, Kolkata, West Bengal 700109, India.
Laboratory of Drug Design and Discovery, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, West Bengal 700032, India.
Comput Biol Chem. 2024 Oct;112:108142. doi: 10.1016/j.compbiolchem.2024.108142. Epub 2024 Jul 2.
This study demonstrated the correlation of molecular structures of Peroxisome proliferator-activated receptor gamma (PPARγ) modulators and their biological activities. Bayesian classification, and recursive partitioning (RP) studies have been applied to a dataset of 323 PPARγ modulators with diverse scaffolds. The results provide a deep insight into the important sub-structural features modulating PPARγ. The molecular docking analysis again confirmed the significance of the identified sub-structural features in the modulation of PPARγ activity. Molecular dynamics simulations further underscored the stability of the complexes formed by investigated modulators with PPARγ. Overall, the integration of many computational approaches unveiled key structural motifs essential for PPARγ modulatory activity that will shed light on the development of effective modulators in the future.
本研究表明，过氧化物酶体增殖物激活受体 γ (PPARγ) 调节剂的分子结构与其生物学活性相关。贝叶斯分类和递归分区 (RP) 研究已应用于包含 323 种不同支架的 PPARγ 调节剂数据集。结果深入了解了调节 PPARγ 的重要亚结构特征。分子对接分析再次证实了所鉴定的亚结构特征在调节 PPARγ 活性中的重要性。分子动力学模拟进一步强调了研究的调节剂与 PPARγ 形成的复合物的稳定性。总体而言，多种计算方法的整合揭示了对 PPARγ 调节活性至关重要的关键结构基序，这将为未来开发有效的调节剂提供启示。
