Bharadwaj Kaushik Kumar, Ahmad Iqrar, Pati Siddhartha, Ghosh Arabinda, Sarkar Tanmay, Rabha Bijuli, Patel Harun, Baishya Debabrat, Edinur Hisham Atan, Abdul Kari Zulhisyam, Ahmad Mohd Zain Muhammad Rajaei, Wan Rosli Wan Ishak
Department of Bioengineering and Technology, Gauhati University, Guwahati, India.
Division of Computer Aided Drug Design, Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, India.
Front Nutr. 2022 Apr 22;9:889276. doi: 10.3389/fnut.2022.889276. eCollection 2022.
The seaweed industries generate considerable amounts of waste that must be appropriately managed. This biomass from marine waste is a rich source of high-value bioactive compounds. Thus, this waste can be adequately utilized by recovering the compounds for therapeutic purposes. Histone deacetylases (HDACs) are key epigenetic regulators established as one of the most promising targets for cancer chemotherapy. In the present study, our objective is to find the HDAC 2 inhibitor. We performed top-down methodologies to identify potential HDAC 2 inhibitors by screening compounds from edible seaweed waste. One hundred ninety-three ( = 193) compounds from edible seaweeds were initially screened and filtered with drug-likeness properties using SwissADME. After that, the filtered compounds were followed to further evaluate their binding potential with HDAC 2 protein by using Glide high throughput virtual screening (HTVS), standard precision (SP), extra precision (XP), and quantum polarized ligand docking (QPLD). One compound with higher negative binding energy was selected, and to validate the binding mode and stability of the complex, molecular dynamics (MD) simulations using Desmond were performed. The complex-binding free energy calculation was performed using molecular mechanics-generalized born surface area (MM-GBSA) calculation. Post-MD simulation analyses such as PCA, DCCM, and free energy landscape were also evaluated. The quantum mechanical and electronic properties of the potential bioactive compounds were assessed using the density functional theory (DFT) study. These findings support the use of marine resources like edible seaweed waste for cancer drug development by using its bioactive compounds. The obtained results encourage further and research. Our findings show that the compound has a high binding affinity for the catalytic site of the HDAC 2 protein and has drug-likeness properties, and can be utilized in drug development against cancer.
海藻产业产生了大量必须妥善管理的废弃物。这种来自海洋废弃物的生物质是高价值生物活性化合物的丰富来源。因此，通过回收这些化合物用于治疗目的，可以充分利用这种废弃物。组蛋白脱乙酰酶（HDACs）是关键的表观遗传调节剂，已被确立为癌症化疗最有前景的靶点之一。在本研究中，我们的目标是寻找HDAC 2抑制剂。我们采用自上而下的方法，通过筛选可食用海藻废弃物中的化合物来鉴定潜在的HDAC 2抑制剂。最初筛选了193种来自可食用海藻的化合物，并使用SwissADME根据类药性质进行过滤。之后，通过使用Glide高通量虚拟筛选（HTVS）、标准精度（SP）、高精度（XP）和量子极化配体对接（QPLD），对过滤后的化合物进一步评估其与HDAC 2蛋白的结合潜力。选择了一种具有更高负结合能的化合物，并使用Desmond进行分子动力学（MD）模拟，以验证复合物的结合模式和稳定性。使用分子力学-广义玻恩表面面积（MM-GBSA）计算进行复合物结合自由能计算。还评估了MD模拟后的分析，如主成分分析（PCA）、动态聚类相关矩阵（DCCM）和自由能景观。使用密度泛函理论（DFT）研究评估潜在生物活性化合物的量子力学和电子性质。这些发现支持利用可食用海藻废弃物等海洋资源，通过其生物活性化合物进行癌症药物开发。所得结果鼓励进一步的深入研究。我们的研究结果表明，该化合物对HDAC 2蛋白的催化位点具有高结合亲和力，具有类药性质，可用于抗癌药物开发。
