纤连蛋白糖蛋白浓度的增加可引起子宫内膜异位症患者的异位组织生长以及各种癌性肿瘤的形成。此外，纤连蛋白与其 EDA（外域 A）区域的受体结合有助于促进肿瘤发生、转移和血管生成。因此，EDA 区域可以被认为是治疗干预的独特靶点。因此，本研究使用计算方法来确定 FDA 批准的药物中最好的纤连蛋白抑制剂。首先，使用 PyRx 0.8 进行基于对接的虚拟筛选。接下来，选择在对接阶段获得良好结果的 FDA 批准的药物，使用分子动力学（MD）模拟进行进一步的研究和分析。虚拟筛选的初步结果显示，FDA批准的17种药物（2471种）具有更有利的能量，其结合能低于-9kcal/mol。这17种药物的MD模拟结果表明，Avapritinib比EDA结构域中的其他复合物具有更低的RMSD值和更高的结合能和氢键。此外，与第二结构变化相关的分析表明，EDA 域中的 Avapritinib 导致了第二结构的更多变化。结果显示，抗癌药物Avapritinib与纤连蛋白形成的复合物比FDA批准的其他药物更稳定。此外，该药物会导致第二个 EDA 结构发生更多变化，这可能具有更严重的抑制 EDA 纤连蛋白的潜力。Ramaswamy H. Sarma 通讯。

Increased concentrations of the fibronectin glycoprotein can cause ectopic tissue growth patients with endometriosis and the formation of various cancerous tumors. Furthermore, fibronectin binding to its receptors from the EDA (Extra Domain A) region contributes to promote tumorigenesis, metastasis and vasculogenesis. Thus, the EDA region can be considered a unique target for therapeutic intervention. Therefore, the present study used computational methods to identify the best fibronectin inhibitor(s) among FDA-approved drugs. First, docking-based virtual screening was performed using PyRx 0.8. Next, FDA-approved drugs that obtained favorable results in the docking phase were selected for further studies and analysis using molecular dynamics (MD) simulation. The preliminary findings of the virtual screening showed that 17 FDA-approved drugs (from 2471) had more favorable energy with their binding energy less than -9 kcal/mol. The MD simulation results of these 17 drugs showed that Avapritinib had a lower RMSD value and higher binding energy and hydrogen bonding than the other complexes in the EDA domain. Also, analyses related to the second structure changes displayed that Avapritinib in the EDA domain led to more changes in the second structure. According to the results, the anticancer drug Avapritinib forms a more stable complex with fibronectin than other FDA-approved drugs. Furthermore, this drug leads to more changes in the second EDA structure, which may have more serious potential for inhibiting EDA fibronectin.Communicated by Ramaswamy H. Sarma.