Volume 13, Issue 52 (9-2023)                   NCMBJ 2023, 13(52): 33-44 | Back to browse issues page

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Afyani F A. Investigation of AKR1C3 protein inhibition mechanism and design of new inhibitors. NCMBJ 2023; 13 (52) :33-44
URL: http://ncmbjpiau.ir/article-1-1584-en.html
Department of Animal Science, Science and Research Branch, Islamic Azad University, Tehran, Iran , Farzad.Atrian@yahoo.com
Abstract:   (492 Views)
Aim and Backgrounds: The AKR1C3 protein plays a very important role in various diseases, especially cancer, and is an attractive target for drug development in hormone-dependent cancers and inflammatory diseases. Therefore, the aim of the present study was to investigate the inhibitory mechanism of AKR1C3 protein and to design new inhibitors.
Materials and methods: In the present study, the three-dimensional structure of AKR1C3 was obtained from the three-dimensional protein structure database using molecular systems. Then, the obtained structure was optimized using the molecular dynamics technique, and then the protein interactions with the existing inhibitors were investigated using the docking technique and Autodock4 software. Then, in order to perform molecular dynamics, AMBER software version 18 was used. Finally, 4 new inhibitor combinations with Data Warrior software were designed as new inhibitors and introduced to inhibit AKR1C3.
Results: The amino acids tyrosine 55 and histidine 117 are involved in the formation of strong hydrogen bonds with the designed inhibitors. The amino acids tyrosine 55, histidine 117, and phenylalanine 311 play an important role in the interaction of proteins with designed inhibitors. The study of binding energy of these compounds to protein showed that the binding energy values ​​of these compounds with AKR1C3 protein are in the range of -17.8 to -29.1 kcal / mol, which can be well competitive with known protein inhibitors. Meanwhile, the structure of D1 as a designed compound with a binding energy of -32.9 kcal / mol was able to show the greatest tendency for protein among the inhibitory compounds known and designed in this study, which can be considered as a compound with a high potential for Introduce inhibition of AKR1C3 protein in laboratory and clinical studies.
Conclusion: The results of docking and molecular dynamics studies showed that the new compounds based on mefenamic acid could be potential compounds to inhibit the AKR1C3 protein, and by making appropriate changes in them, these target compounds could be used as effective compounds to inhibit and fight disease. Used inflammatory disease sentence.
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Type of Study: Research Article | Subject: Physiology
Received: 2023/03/14 | Accepted: 2023/09/23 | Published: 2023/10/21

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