Abstract：
Recently tetraspanin CD151 has been identified as an important biological target involved in metastatic processes which include cell adhesion, tumor progression processes, and so forth in different types of cancers, such as breast cancer and glioblastoma. This in Silico study considered 1603 compounds from the Food and Drug Administration database, after performing an ADMET analysis; we selected 853 ligands, which were used for docking analysis. The most promising ligands were selected from docking studies, based on two criteria: (a) showed lowest affinity to the CD151 protein and (b) they interact with the QRD motif, located in the second extracellular loop. Furthermore, we investigate the stability of the protein-ligand complexes through MD simulations as well as free energy MM-PBSA calculations. From these results, loperamide and glipizide were identified as the best evaluated drugs. We suggest an in vitro analysis is needed to confirm our in silico prediction studies.
摘要：
最近，四跨膜蛋白CD151已被确定为参与包括细胞粘附在内的转移过程的重要生物学靶标。肿瘤进展过程，在不同类型的癌症中，如乳腺癌和胶质母细胞瘤。这在Silico研究中考虑了来自食品和药物管理局数据库的1603种化合物，在进行ADMET分析后，我们选择了853个配体，用于对接分析。最有前途的配体是从对接研究中选出的，基于两个标准：（a）对CD151蛋白的亲和力最低，（b）它们与QRD基序相互作用，位于第二个胞外环。此外，我们通过MD模拟以及自由能MM-PBSA计算研究了蛋白质-配体复合物的稳定性。从这些结果来看,洛哌丁胺和格列吡嗪被确定为评价最好的药物。我们建议需要进行体外分析以确认我们的计算机模拟预测研究。
