Crizotinib and Temozolomide are the two major chemotherapy drugs used for the treatment of cancers. Crizotinib is used as a target chemotherapy drug in many cancers. It mainly binds on the ATP binding regions of receptor tyrosine kinases (RTKs) targets and inhibits protein phosphorylation, which has already been reported. Temozolomide drug is known as the alkylating agent. Its mechanism of action is the methylation of DNA and thereby inhibiting DNA replication. However, the Temozolomide drug with protein level interaction of Glioblastoma Multiforme (GBM) and Non-small-cell lung carcinoma (NSCLC) of RTKs targets has not been reported so far. In the proposed work, we investigated the molecular level interaction of the Temozolomide drug in C-MET, C-ROS1, and ALK RTKs targets of GBM and NSCLC using an in silico study. We performed comparative analysis studies in both drugs' docked complexes based on their drug properties and complex energy (CE) to identify the better efficacy of the drug. From the docking studies, we could identify that the Temozolomide drug bounded protein complexes showed the least complex energy. The most stable complexes were identified from these docking studies by Molecular Dynamic simulation. In the proposed study, we found that the docked complex attained a stable conformation and least energy via solid hydrogen bond interactions between the amino acid residues and the drug at the binding sites of the proteins. The least energy and the hydrogen bond interaction of Temozolomide drug with the amino acid residues of the protein complexes of C-MET, C-ROS1 and ALK protein with their id name are: 2WGJ is − 11305.0830 (PRO1158, MET1160), 3ZBF is − 11,659.6814 (MET2029, GLU2027), and 2XP2 is − 11,734.7565 (ARG1275, ASP 1160, GLU1167). Our studies revealed that the Temozolomide drug bounded protein complex showed the least energy when compared to Crizotinib. So it will give better interaction on the binding sites of proteins and thereby provide better inhibition in the treatment of target therapy of GBM and NSCLC.

中文翻译：

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克唑替尼和替莫唑胺药物与胶质母细胞瘤和NSCLC靶点的对接和动态模拟研究，以确定更好的药物疗效

克唑替尼和替莫唑胺是用于治疗癌症的两种主要化疗药物。克唑替尼被用作许多癌症的靶向化疗药物。它主要结合受体酪氨酸激酶 (RTK) 靶标的 ATP 结合区并抑制蛋白质磷酸化，这已被报道。替莫唑胺药物被称为烷化剂。其作用机制是使 DNA 甲基化，从而抑制 DNA 复制。然而，目前尚未报道具有蛋白水平相互作用的多形性胶质母细胞瘤（GBM）和非小细胞肺癌（NSCLC）靶点的替莫唑胺药物。在拟议的工作中，我们使用计算机研究调查了替莫唑胺药物在 GBM 和 NSCLC 的 C-MET、C-ROS1 和 ALK RTKs 靶标中的分子水平相互作用。我们根据药物特性和复合能 (CE) 对两种药物的对接复合物进行了比较分析研究，以确定药物的更好疗效。从对接研究中，我们可以确定 Temozolomide 药物结合的蛋白质复合物表现出最少的复杂能量。通过分子动力学模拟从这些对接研究中鉴定出最稳定的复合物。在拟议的研究中，我们发现对接复合物通过氨基酸残基与蛋白质结合位点的药物之间的固体氢键相互作用获得稳定的构象和最低的能量。Temozolomide 药物与 C-MET、C-ROS1 和 ALK 蛋白的蛋白质复合物的氨基酸残基的最小能量和氢键相互作用，其 id 名称为：2WGJ 为 - 11305.0830 (PRO1158, MET1160)，3ZBF 为 − 11,659.6814（MET2029、GLU2027），2XP2 为 − 11,734.7565（ARG1275、ASP 1160、GLU1167）。我们的研究表明，与克唑替尼相比，替莫唑胺药物结合蛋白复合物的能量最低。因此它将在蛋白质结合位点上产生更好的相互作用，从而在GBM和NSCLC的靶向治疗的治疗中提供更好的抑制。