Investigation of a Stable Interaction of Levothyroxine with AFP Through Molecular Modelling

Emel Akbaba; Deniz Karataş; Ataman Gönel; Ezgi Soylu; Beste Kiraz; Yusur Ammar Almahdi

doi:10.17776/csj.1599148

EN TR

Investigation of a Stable Interaction of Levothyroxine with AFP Through Molecular Modelling

Abstract

Thyroid dysfunctions are common all over the world, and accordingly, the use of thyroid drugs has increased. Incorrect measurement of tumor markers may lead to missed cases of cancer. The most used cancer markers are CA19-9, CA125, CEA, PSA, and AFP molecules. In this study, the molecular interactions of these markers with the thyroid medications of levothyroxine, methimazole, and propylthiouracil were investigated via molecular docking and dynamics simulations. In the molecular docking studies, levothyroxine was shown to interact with AFP, CEA, and CA15-3 in low concentrations. As a result of the MD simulations, the AFP/LEVO model exhibited the highest level of interaction. For instance, while the RMSD values of AFP/Levothyroxine complex were consistently around 0.7, and for the others they were observed above 1. This tight binding was reflected in interaction energies, with the total interaction in the AFP/Levothyroxine model computed as -192.04 kJ/mol. In contrast, for CA15-3/Levothyroxine and CEA/Levothyroxine complexes, these values were calculated as -135.26 and -88.56 kJ/mol, respectively. The SASA analysis also suggested the superiority of AFP/Levothyroxine complex due to ligand masking and a decrease in standard deviation, as the SASA mean difference area was found to be -0.46.

Keywords

Moleküler Modelleme Yoluyla Levotiroksinin AFP ile Kararlı Bir Etkileşiminin Araştırılması

Öz

Tiroid disfonksiyonları tüm dünyada yaygındır ve buna bağlı olarak tiroid ilaçlarının kullanımı artmıştır. Tümör belirteçlerinin yanlış ölçülmesi kanser vakalarının gözden kaçmasına yol açabilir. En çok kullanılan kanser belirteçleri CA19-9, CA125, CEA, PSA ve AFP molekülleridir. Bu çalışmada, bu belirteçlerin tiroid ilaçları olan levotiroksin, metimazol ve propiltiyourasil ile moleküler etkileşimleri moleküler yerleştirme ve dinamik simülasyonları yoluyla araştırılmıştır. Moleküler yerleştirme çalışmalarında, levotiroksinin düşük konsantrasyonlarda AFP, CEA ve CA15-3 ile etkileşime girdiği gösterilmiştir. MD simülasyonları sonucunda, AFP/LEVO modeli en yüksek etkileşim seviyesini göstermiştir. Örneğin, AFP/Levotiroksin kompleksinin RMSD değerleri sürekli olarak 0,7 civarındayken, diğerleri için 1'in üzerinde gözlendi. Bu sıkı bağlanma etkileşim enerjilerine yansıdı ve AFP/Levotiroksin modelindeki toplam etkileşim -192,04 kJ/mol olarak hesaplandı. Buna karşılık, CA15-3/Levotiroksin ve CEA/Levotiroksin kompleksleri için bu değerler sırasıyla -135,26 ve -88,56 kJ/mol olarak hesaplandı. SASA analizi ayrıca, ligand maskelemesi ve standart sapmadaki azalma nedeniyle AFP/Levotiroksin kompleksinin üstünlüğünü de önerdi, çünkü SASA ortalama fark alanı -0,46 olarak bulundu.

Anahtar Kelimeler

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Details

Primary Language

English

Subjects

Molecular Docking , Computational Chemistry , Bioengineering (Other)

Journal Section

Research Article

Authors

Emel Akbaba
0000-0003-4915-5153
Türkiye

Deniz Karataş ^*
0000-0002-8176-4883
Türkiye

Ataman Gönel
0000-0001-7200-1537
Türkiye

Ezgi Soylu
0000-0003-1322-580X
Türkiye

Beste Kiraz
0009-0003-0125-8791
Türkiye

Yusur Ammar Almahdi
0009-0003-9569-3777
Türkiye

Publication Date

June 30, 2025

Submission Date

December 12, 2024

Acceptance Date

May 19, 2025

Published in Issue

Year 2025 Volume: 46 Number: 2

DOI

https://doi.org/10.17776/csj.1599148

IZ

https://izlik.org/JA84RE58EL

Cite

RIS / Bibtex

APA

Akbaba, E., Karataş, D., Gönel, A., Soylu, E., Kiraz, B., & Almahdi, Y. A. (2025). Investigation of a Stable Interaction of Levothyroxine with AFP Through Molecular Modelling. Cumhuriyet Science Journal, 46(2), 274-285. https://doi.org/10.17776/csj.1599148