Shamsara Jamal
Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Int J Comput Biol Drug Des. 2014;7(1):80-95. doi: 10.1504/IJCBDD.2014.058594. Epub 2014 Jan 9.
MIA (Melanoma Inhibitory Activity) protein is over expressed in melanoma cells and binds to extracellular matrix proteins as well as to several integrins. These interactions were suggested to promote formation of metastasis. Therefore, abrogation of MIA interaction with other proteins using small molecules might show a diminishing effect on cancer cell invasion. The present study is aimed at the analysis of the integrin-binding site of MIA using molecular docking, followed by a virtual screening for drug-like compounds that show potential as putative inhibitors of MIA-integrin interaction. Results showed that at the proposed binding interface of the MIA-integrin complex, a druggable binding pocket is located. Therefore, the integrin-binding domain of MIA was used as a receptor to screen 2200 drug-like compounds. Next, we analysed the interactions of the identified hit compounds with the MIA binding pocket to find the most important features of the hit compounds.
黑色素瘤抑制活性（MIA）蛋白在黑色素瘤细胞中过度表达，并与细胞外基质蛋白以及几种整合素结合。这些相互作用被认为会促进转移的形成。因此，使用小分子消除MIA与其他蛋白质的相互作用可能会对癌细胞侵袭产生抑制作用。本研究旨在通过分子对接分析MIA的整合素结合位点，随后对具有作为MIA-整合素相互作用假定抑制剂潜力的类药物化合物进行虚拟筛选。结果表明，在MIA-整合素复合物的拟结合界面处，存在一个可成药的结合口袋。因此，将MIA的整合素结合域用作受体来筛选2200种类药物化合物。接下来，我们分析了所鉴定的命中化合物与MIA结合口袋的相互作用，以找出命中化合物的最重要特征。
