A review of MMP-2 structures and binding mode analysis of its inhibitors to strategize structure-based drug design. (15th November 2022)

• Record Type: Journal Article
• Authors: Sanyal, Saptarshi; Amin, Sk. Abdul; Banerjee, Priyanka; Gayen, Shovanlal; Jha, Tarun
• Is Part Of: Bioorganic & medicinal chemistry. Volume 74(2022)
• Publication Date: 2022-11-15
• Subjects: Cancer -- MMP-2 -- SBDD -- Molecular modeling -- Docking -- Molecular dynamic simulation; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2022.117044
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Highlight: Matrix metalloproteinase-2 has been a target of choice for the drug development. Different NMR and X-ray crystallographic structures reported for MMP-2 are analysed in details. An exquisite picture of the structure-based drug design (SBDD) approaches of MMP-2 inhibitors is provided. This study delineates plausible strategies for designing specific MMP-2 inhibitor. Abstract: 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.