School of Medical Sciences, Adamas University, Barasat, West Bengal, India; Natural Science Laboratory, Division of Medicinal Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, West Bengal, India.
Natural Science Laboratory, Division of Medicinal Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, West Bengal, India; Department of Pharmaceutical Technology, JIS University, 81, Nilgunj Road, Agarpara, Kolkata, West Bengal, India.
Bioorg Med Chem. 2022 Nov 15;74:117044. doi: 10.1016/j.bmc.2022.117044. Epub 2022 Oct 4.
The protease enzyme, matrix metalloproteinase-2 (MMP-2) has been a target of choice for the drug development due to its multi-façade involvement in numerous diseased conditions including cancer. To find a selective MMP-2 inhibitor several computational strategies are employed in its design and discovery. In these strategies, protein structure of MMP-2 is an inevitable part to formulate effective structure-based drug design (SBDD) of selective MMP-2 inhibitors. In the present communication, several crystal structures of MMP-2 have been analyzed with different statistical parameters and their implementations in SBDD of inhibitors are scrutinized. In addition, binding mode analyses of various classes of inhibitors are discussed to pinpoint the effective design of selective inhibitors by maximizing its interaction with the MMP-2 enzyme binding site. This may provide a crucial insight for exploring the numerous possibilities for SBDD of MMP-2 inhibitors to accelerate anticancer drug discovery efforts.
蛋白酶酶，基质金属蛋白酶-2（MMP-2）一直是药物开发的首选目标，因为它在包括癌症在内的多种疾病中的多方面参与。为了找到选择性 MMP-2 抑制剂，在其设计和发现中采用了几种计算策略。在这些策略中，MMP-2 的蛋白质结构是制定有效的基于结构的药物设计（SBDD）选择性 MMP-2 抑制剂的必要部分。在本通讯中，分析了 MMP-2 的几种晶体结构，并使用不同的统计参数对其在抑制剂的 SBDD 中的应用进行了研究。此外，还讨论了各种类抑制剂的结合模式分析，以通过最大化其与 MMP-2 酶结合位点的相互作用来确定选择性抑制剂的有效设计。这可能为探索 SBDD 选择性 MMP-2 抑制剂的众多可能性提供重要的见解，以加速抗癌药物的发现。
