Abdul Rashid, Nur Nadiah and Mohd Nasir, Mohd Hamzah and Hamzah, Nurasyikin and Ismail, Che Muhammad Khairul Hisyam and Nor Hishamuddin, Siti Aishah Sufira and Mohamed Suffian, Izzat Fahimuddin and Abdul Hamid, Azzmer Azzar (2024) Three-dimensional structure of Human Epididymis Protein 4 (HE4): a protein modelling of an ovarian cancer biomarker through in silico approach. Journal of Tropical Life Science, 14 (2). pp. 331-348. ISSN 2087-5517 E-ISSN 2527-4376
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Abstract
The Human Epididymis Protein 4 (HE4) biomarker has been extensively investi-gated for its potential in diagnosing ovarian cancer (OC). For the application of di-agnostic techniques and drug delivery, it is crucial to understand the protein tertiary structure. However, the Protein Data Bank (PDB) does not currently contain the three-dimensional (3D) structure of HE4. Therefore, an in silicoanalysis was con-ducted to model the HE4 protein using AlphaFold, I-TASSER, and Robetta servers, with the sequence retrieved from UniProt (ID: Q14508). These three servers em-ployed deep learning algorithms, threading templates, and de novomethods, respec-tively. Subsequently, Molecular Dynamics (MD) simulation using the GROMACS software package improved each 3D structure model, resulting in optimised and re-fined structures: RF1, RF2, and RF3. PROCHECK and ERRAT programmes were employed to assess the structure quality. The Ramachandran plots from PROCHECK indicated that 100% of residues were within the allowed regions for all servers except for I-TASSER. For the refined structures, RF1 and RF3, all residues were concentrated within the allowed regions. According to the ERRAT programme, the RF1 model exhibited the highest overall quality factor of 97.701, followed by RF3 and AlphaFold models with scores of 94.643 and 93.750, respectively. After these validations, RF1 emerged as the most accurately predicted 3D structure of HE4 and has one tunnel identified by CAVER 3.0 tool that facilitates the transportation of small particles to theactive site, supported by FTsite and PrankWeb binding site predictions. This model holds potential for various computational studies, including the development of OC diagnostic kits. It will enhance our comprehension of the interactions between the protein and other biomolecules
| Item Type: | Article (Journal) |
|---|---|
| Uncontrolled Keywords: | AlphaFold, De novo, Human Epididymis Protein 4 (HE4), Ramachan-dran plot, Threading template |
| Subjects: | Q Science > Q Science (General) |
| Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button): | Centre for Foundation Studies Kulliyyah of Pharmacy Kulliyyah of Pharmacy > Department of Pharmaceutical Technology Kulliyyah of Science Kulliyyah of Science > Department of Biotechnology Kulliyyah of Science > Department of Chemistry |
| Depositing User: | Dr Mohd Hamzah Mohd Nasir |
| Date Deposited: | 11 Jul 2024 11:38 |
| Last Modified: | 11 Jul 2024 14:39 |
| URI: | http://irep.iium.edu.my/id/eprint/113071 |
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