Abstract：
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).Communicated by Ramaswamy H. Sarma.
摘要：
NIMA相关激酶7（NEK7）和磷蛋白磷酸酶-1催化亚基α（PPP1CA）是胰腺导管腺癌中最常见的过表达蛋白，这是最常见的胰腺癌。本研究的目的是确定一种可能的NEK7和PPP1CA治疗性抑制剂。为了这次调查,从IMPPAT植物化学物质库中检索到5000种化合物，与我们各自的目标蛋白对接。此外，参考化合物，吉西他滨,这是美国食品和药物管理局（FDA）批准的药物，与靶蛋白对接。两种靶向蛋白质的参考化合物的结合能为-6.5kcal/mol。对于两个靶标具有最低结合能的常见配体是boeravinoneB（PubChemID：14018348），NEK7为-9.2kcal/mol，PPP1CA为-7.6kcal/mol。通过密度泛函理论(DFT)和分子动力学模拟分析进一步研究了该化合物。均方根偏差(RMSD)，均方根波动(RMSF)，回转半径(Rg),和氢键分析表明boeravinoneB与靶蛋白（NEK7和PPP1CA）的稳定性。由RamaswamyH.Sarma沟通。
