Short Communication - Der Pharmacia Lettre ( 2024) Volume 16, Issue 2
Received: 30-Jan-2024, Manuscript No. DPL-24-129643;
Editor assigned: 01-Feb-2024, Pre QC No. DPL-24-129643 (PQ);
Reviewed: 15-Feb-2024, QC No. DPL-24-129643;
Revised: 22-Feb-2024, Manuscript No. DPL-24-129643 (R);
Published:
01-Mar-2024
, DOI: 10.37532/dpl.2024.16.19
, Citations: Botha J 2024. The Role of Chemical Components for the Mirk Receptor via Molecular Simulation. Der Pharma Lett.16:19-20.
,
Copyright: © 2024 Botha J. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Impaired apoptosis and unchecked proliferation are two characteristics of cancer. One of the main diseases that kill people worldwide and a significant health issue is cancer. The Dual-Specificity Tyrosine-Phosphorylation-Regulated Kinase (Dyrk) family includes Mirk/Dyrk1B. There are four distinct isoforms found in it, including Dyrk1B, Dyrk2, Dyrk3, and Dyrk4. According to a number of researches, Dyrk1B is essential for both muscle differentiation and cancer biology. Because it may auto phosphorylate serine and/or threonine, it is also known as a dual function kinase. While Mirk/Dyrk1B is strongly expressed in various solid tumours, including lung cancer, and is expressed at a low level in normal tissues, it is known to mediate cell survival and differentiation in these conditions.
By lowering the production of harmful ROS and increasing the expression of the antioxidant gene in cancer cells, it helps these cells survive. It also possesses the peculiar quality of being most active in cancer cells that are dormant. Numerous clinical disorders, including cancer, can result from genetic alterations such as mutations, translocations, and amplifications. When the amplified genes allow for selective growth, amplicons are preserved in cancer cells. According to a recent study, Mirk is one of 16 genes found in a 660 kb sub-region of the 19q13 amplicon that is regularly amplified in ovarian and pancreatic cancers. The majority of cancer cells retain these amplicons, which offer a selective growth or survival advantage. The tiny protein kinase protein Dryk1B may have a direct connection to cancer. From cell division to cell differentiation, Dyrk1B expression increases significantly; yet, the mechanisms governing these processes remain poorly understood. Many studies have been conducted in recent years to determine how knockdown of Mirk/Dyrk1B affects apoptosis and how it raises the sensitivity of different cancer cells. Lung cancer cells are more likely to survive when mirk is overexpressed. Additionally, it increases the survival of developing myoblasts by phosphorylating the CDK inhibitors p21, which causes p21 to accumulate in the cytoplasm and function as a signaling molecule that prevents apoptosis.
As a result, Mirk/Dyrk1B serves as a cutting-edge therapeutic target to stop cancer. In cancer cells, mutations often do not raise the Mirk activity. However, when the cells undergo quiescence and exit the cell, as well as when they are exposed to chemotherapeutic agents such as 5-Fu and cisplatin, the Mirk activity increases dramatically, often several times over. The Dyrk kinases are categorized as dual function kinases because they have the ability to phosphorylate both serine and threonine as well as auto phosphorylate tyrosine during the translation process. The expression of Mirk/Dyrk1B was found to be low in both lung cancer and normal colon tissues. Numerous research investigations have established the pivotal role that the Mirk plays in regulating transcription, cell cycle, and mortality. Therefore, the goal of the current study is to identify possible Mirk inhibitors using a computational method. Since the 3-dimensional structure of Mirk was not available, a molecular modeling approach was used to model the structure. Using the phase module implemented in Schrodinger, virtual screening against the modeled structure was carried out, and molecular docking and simulation were used to assess the stability and interaction of lead molecules with active site residues, respectively. Additionally, the Qikprop module was used to verify the drug-likeness characteristics of the lead compounds that had been screened.
The Schrodinger sitemap algorithm was able to anticipate the active site of the modeled Mirk. For additional virtual screening, the centroid of the binding region's active site residues was taken into consideration when creating the grid. Potential inhibitors were located using the Chembridge database. In Schrodinger LLC, 2018, the verified Mirk model and the ligands from the Chembridge database were loaded. Before docking, the LigPrep module in maestro was used to extend the protonation and tautomeric states of each ligand molecule at 7.0 pH. Lipinski's criterion was not followed by the ligand or the high energy tautomer state or ionization state, or the molecules with reactive functional groups were removed from the created confirmation. All of the top-ranked compounds found through docking experiments also showed strong hydrogen bond interactions with the amino acid residues Asn86, Lue83, and Ile7, with stable and strong interactions occurring within the allotted period in the molecular dynamics simulation trajectory.
Citation: Botha J 2024. The Role of Chemical Components for the Mirk Receptor via Molecular Simulation. Der Pharma Lett.16:19-20.
Copyright: © 2024 Botha J. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
