Adrees Safa, Imtiaz Anam, Yaseen Aiman, Irfan Fareed Muhammad, Anwar Waqar, Ashraf Asma, Shabbir Rana Muhammad Kamran, Andlib Shaista, Hussain Mureed, Tariq Asma, Mateen Rana Muhammad, Saqib Muhammad Arif Nadeem, Parveen Rukhsana
Department of Life sciences, School of Science, University of Management and Technology, Lahore, Pakistan.
Department of Zoology, Division of science and Technology, University of Education, Lahore, Pakistan.
J Biomol Struct Dyn. 2024 Mar 12:1-17. doi: 10.1080/07391102.2024.2318484.
NIMA-related kinase 7 (NEK7) and phosphoprotein phosphatase-1 catalytic subunit alpha (PPP1CA) are the most common proteins overexpressed in pancreatic ductal adenocarcinoma, which is the most common type of pancreatic cancer. The goal of the current study was to identify a possible NEK7 and PPP1CA therapeutic inhibitor. For this investigation, 5000 compounds were retrieved from the IMPPAT library of phytochemicals, which were docked with our respective target proteins. Also, a reference compound, gemcitabine, which is a Food and Drug Administration (FDA) approved drug, was docked with the target proteins. The binding energy of the reference compound for both the targeted proteins was -6.5 kcal/mol. The common ligand with the lowest binding energy for both targets is boeravinone B (PubChem ID: 14018348) with -9.2 kcal/mol of NEK7 and -7.6 kcal/mol for PPP1CA. The compound was further investigated through density function theory (DFT) and molecular dynamic simulation analysis. The root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), and hydrogen bonding analysis indicated the stability of the boeravinone B with the target proteins (NEK7 and PPP1CA).
NIMA相关激酶7（NEK7）和磷酸蛋白磷酸酶-1催化亚基α（PPP1CA）是胰腺导管腺癌中最常见的过表达蛋白，胰腺导管腺癌是胰腺癌最常见的类型。本研究的目的是确定一种可能的NEK7和PPP1CA治疗抑制剂。为了进行这项研究，从植物化学物质的IMPPAT库中检索了5000种化合物，并将它们与我们各自的目标蛋白进行对接。此外，一种参考化合物吉西他滨，它是一种美国食品药品监督管理局（FDA）批准的药物，也与目标蛋白进行了对接。参考化合物与两种目标蛋白的结合能为-6.5千卡/摩尔。两种靶点结合能最低的共同配体是波拉维酮B（PubChem ID：14018348），与NEK7的结合能为-9.2千卡/摩尔，与PPP1CA的结合能为-7.6千卡/摩尔。通过密度泛函理论（DFT）和分子动力学模拟分析对该化合物进行了进一步研究。均方根偏差（RMSD）、均方根波动（RMSF）、回转半径（Rg）和氢键分析表明波拉维酮B与目标蛋白（NEK7和PPP1CA）具有稳定性。
