Laboratory of Drug Design and Discovery, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad, India.
J Biomol Struct Dyn. 2024 Jul;42(11):5642-5656. doi: 10.1080/07391102.2023.2227710. Epub 2023 Jun 26.
Histone deacetylase 1 (HDAC1), a class I HDAC enzyme, is crucial for histone modification. Currently, it is emerged as one of the important biological targets for designing small molecule drugs through cancer epigenetics. Along with synthetic inhibitors different natural inhibitors are showing potential HDAC1 inhibitions. In order to gain insights into the relationship between the molecular structures of the natural inhibitors and HDAC1, different molecular modelling techniques (Bayesian classification, recursive partitioning, molecular docking and molecular dynamics simulations) have been applied on a dataset of 155 HDAC1 nature-inspired inhibitors with diverse scaffolds. The Bayesian study showed acceptable values for both the training set and test sets. The Recursive partitioning study produced decision tree 1 with 6 leaves. Further, molecular docking study was processed for generating the protein ligand complex which identified some potential amino acid residues such as F205, H28, L271, P29, F150, Y204 for the binding interactions in case of natural inhibitors. Stability of these HDAC1-natutal inhibitors complexes has been also evaluated by molecular dynamics simulation study. The current modelling study is an attempt to get a deep insight into the different important structural fingerprints among different natural compounds modulating HDAC1 inhibition.Communicated by Ramaswamy H. Sarma.
组蛋白去乙酰化酶 1（HDAC1）是 I 类 HDAC 酶，对于组蛋白修饰至关重要。目前，它已成为通过癌症表观遗传学设计小分子药物的重要生物靶标之一。除了合成抑制剂外，不同的天然抑制剂也表现出对 HDAC1 的潜在抑制作用。为了深入了解天然抑制剂的分子结构与 HDAC1 之间的关系，我们应用了不同的分子建模技术（贝叶斯分类、递归分区、分子对接和分子动力学模拟），对具有不同支架的 155 种 HDAC1 天然抑制剂的数据集进行了分析。贝叶斯研究对训练集和测试集都显示出了可接受的值。递归分区研究生成了具有 6 个叶的决策树 1。此外，我们还进行了分子对接研究，生成了蛋白质-配体复合物，确定了一些潜在的氨基酸残基，如 F205、H28、L271、P29、F150、Y204，它们在天然抑制剂结合相互作用中发挥作用。我们还通过分子动力学模拟研究评估了这些 HDAC1-天然抑制剂复合物的稳定性。目前的建模研究旨在深入了解不同天然化合物调节 HDAC1 抑制作用的不同重要结构指纹。由 Ramaswamy H. Sarma 交流。
