A review of MMP-2 structures and binding mode analysis of its inhibitors to strategize structure-based drug design

Saptarshi Sanyal; Sk Abdul Amin; Priyanka Banerjee; Shovanlal Gayen; Tarun Jha

doi:10.1016/j.bmc.2022.117044

A review of MMP-2 structures and binding mode analysis of its inhibitors to strategize structure-based drug design

Bioorg Med Chem. 2022 Nov 15:74:117044. doi: 10.1016/j.bmc.2022.117044. Epub 2022 Oct 4.

Authors

Saptarshi Sanyal¹, Sk Abdul Amin², Priyanka Banerjee³, Shovanlal Gayen⁴, Tarun Jha⁵

Affiliations

¹ 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.
² 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. Electronic address: pharmacist.amin@gmail.com.
³ School of Medical Sciences, Adamas University, Barasat, West Bengal, India.
⁴ Laboratory of Drug Design and Discovery, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, West Bengal, India. Electronic address: shovanlal.gayen@gmail.com.
⁵ Natural Science Laboratory, Division of Medicinal Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, West Bengal, India. Electronic address: tjupharm@yahoo.com.

PMID: 36244233
DOI: 10.1016/j.bmc.2022.117044

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.

Keywords: Cancer; Docking; MMP-2; Molecular dynamic simulation; Molecular modeling; SBDD.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Drug Design
Matrix Metalloproteinase 2* / metabolism
Matrix Metalloproteinase Inhibitors / chemistry
Molecular Docking Simulation
Molecular Dynamics Simulation*

Substances

Matrix Metalloproteinase 2
Matrix Metalloproteinase Inhibitors