Molecular dynamics dataset for pharmacological repositioning in the treatment of non-small-cell lung cancer

Non-small cell lung cancer (NSCLC) is a type of lung cancer associated with translocation of the EML4 and ALK genes on the short arm of chromosome 2. This leads to the development of an aberrant protein kinase with a deregulated catalytic domain, the cdALK+. Currently, different ALK inhibitors (iALKs) have been proposed to treat ALK+ NSCLC patients. However, the recent resistance to iALKs stimulates the exploration of new iALKs for NSCLC. Here, we describe an in silico approach to finding FDA-approved drugs that can be used by pharmacological repositioning as iALK. We used homology modelling to obtain a structural model of cdALK+ protein and then performed molecular docking and molecular dynamics of the complex cdALK+-iALKs to generate the pharmacophore model. The pharmacophore was used to identify potential iALKs from FDA-approved drugs library by ligand-based virtual screening. Four pharmacophores with different atomistic characteristics were generated, resulting in six drugs that sat..., Was used YASARA™ software to perform the simulations between the interactions of the cdALK+ with ATP and its known inhibitors: crizotinib, ceritinib, brigatinib, alectinib, lorlatinib.  The force fields used in the molecular dynamics, was AMBER14.
 , , # Molecular Dynamics DataSet for pharmacological repositioning in the treatment of non-small-cell lung cancer.

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The presented database comprises files in \".tab\" format, containing information pertaining to the molecular dynamics of the complex formed by the catalytic domain of ALK with the drugs under study. YASARA software was utilized for data acquisition, employing the AMBER 14 force field for molecular dynamics. A periodic cubic box, extending 20 Å around the complex, was generated. Physiological pH configurations at 7.4 and 0.9% NaCl for ion concentration as a mass fraction were applied.The system simulation was neutralized with TIP3P water molecules as a solvent, maintaining a density of 0.997 g/l. The simulation parameters included a temperature of 298 K, a pressure of 1 atm, and coulomb electrostatics with a cutoff of 8 Å, the default used by AMBER. The simulation time step was set at 2 ft, with each trajectory saved at 100 ps intervals. Subsequently, anal...

非小细胞肺癌（Non-small cell lung cancer, NSCLC）是一类与2号染色体短臂上EML4与ALK基因易位相关的肺癌亚型。该基因易位会诱导产生带有失调催化结构域的异常蛋白激酶cdALK+。目前，多款间变性淋巴瘤激酶抑制剂（ALK inhibitors, iALKs）已被提出用于治疗ALK阳性非小细胞肺癌患者。然而，近年来临床中出现的ALK抑制剂耐药问题，推动了新型ALK抑制剂的研发探索。本研究介绍了一种计算机虚拟筛选方法，通过药物重定位策略从美国食品药品监督管理局（Food and Drug Administration, FDA）批准上市的药物库中筛选潜在ALK抑制剂。我们首先通过同源建模技术获得cdALK+蛋白的结构模型，随后对cdALK+与ALK抑制剂的复合物开展分子对接与分子动力学模拟，以构建药效团模型。基于该药效团模型，我们通过配体基虚拟筛选从FDA批准药物库中识别潜在的ALK抑制剂。本研究共构建了四种具有不同原子特征的药效团，最终筛选得到六种符合条件的药物……本研究使用YASARA™软件完成了cdALK+与三磷酸腺苷（adenosine triphosphate, ATP）及其已知抑制剂（克唑替尼、色瑞替尼、布加替尼、阿来替尼、洛拉替尼）之间相互作用的模拟实验。分子动力学模拟所采用的力场为AMBER14。

# 用于非小细胞肺癌药物重定位治疗的分子动力学数据集
DOI: dryad.ttdz08m4m

本数据集包含格式为".tab"的文件，记录了ALK催化结构域与本次研究中受试药物形成的复合物的分子动力学相关信息。本研究采用YASARA软件进行数据采集，分子动力学模拟使用AMBER 14力场。我们构建了将复合物包围在内的周期性立方盒子，盒子边缘距离复合物的距离为20埃（Å）。模拟体系采用生理条件配置：pH值为7.4，离子浓度为质量分数0.9%的氯化钠溶液。体系使用TIP3P水分子作为溶剂以维持电中性，溶剂密度维持在0.997 g/L。模拟参数设置如下：温度298 K，压力1 atm，库仑静电相互作用采用AMBER默认的8埃截断半径。模拟时间步长设置为2飞秒（原文疑似笔误，原标注为“2 ft”，结合分子动力学模拟常规参数应为“2 fs”），每条轨迹以100皮秒（ps）的间隔进行保存。后续分析……