Sains Malaysiana 49(3)(2020): 517-525

http://dx.doi.org/10.17576/jsm-2020-4903-06

Exploring the Molecular Interactions between Neoculin and the Human Sweet Taste Receptors through Computational Approaches

(Meneroka Interaksi Molekul antara Neokulin dan Reseptor Rasa Manis Manusia melalui Pendekatan Pengiraan)

RAGHEED HUSSAM YOUSIF¹, HABIBAH A. WAHAB², KAMYAR SHAMELI¹ & NURUL BAHIYAH AHMAD KHAIRUDIN¹*

¹Department of Environment and Green Technology, Malaysia-Japan International Institute of Technology, Universiti Teknologi Malaysia, Jalan Sultan Yahya Petra, 54100 Kuala Lumpur, Federal Territory, Malaysia

²School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Universiti Sains Malaysia, Pulau Pinang, Malaysia

Diserahkan: 24 Mei 2019/Diterima: 5 Disember 2019

ABSTRACT

Neoculin is a sweet taste protein capable of modifying sour taste into sweet taste. Neoculin, along with other sweeteners, are received by the human sweet taste receptors T1R2 and T1R3. To date, there has been few studies regarding how neoculin interacts with the human sweet taste receptors in molecular level. In this study, computational approaches were applied to elucidate how neoculin interact with T1R2 and T1R3 at molecular level. In order to achieve this research, homology modeling for T1R2 and T1R3 was performed to predict their structure. A protein-protein docking study was conducted between neoculin and T1R2 and T1R3, which displayed a strong relationship with the previous experimental findings regarding the important residues of neoculin, and how they interact with the ATD domain of T1R3. These residues are His11, Asp91, Tyr21, Asn44, Arg48, Tyr 65, Val72, and Phe94. The best docked complexes were then subjected to molecular dynamics simulation for further analysis. The molecular dynamics simulation results showed the contributions of the important residues of neoculin in forming hydrogen bonds with the residues of the receptors. The binding energy between neoculin and each of T1R2 and T1R3 were also calculated. These results concluded that neoculin sweet taste and taste modifying abilities are only active when it binds to the amino terminal domain of T1R3.

Keywords: Homology modeling; molecular dynamics simulation; neoculin; protein-protein docking; T1R2\T1R3

ABSTRAK

Neokulin adalah protein rasa manis yang mampu mengubah rasa masam menjadi rasa manis. Neokulin, seperti pemanis lain, diterima oleh reseptor perasa manis manusia iaitu T1R2 dan T1R3. Sehingga kini, sudah terdapat beberapa kajian yang dijalankan untuk mengenal pasti bagaimana neokulin berinteraksi dengan reseptor kemanisan pada peringkat molekul. Dalam kajian ini, kaedah pengiraan digunakan untuk memperjelaskan bagaimana neokulin berinteraksi dengan T1R2 dan T1R3 pada tahap molekul. Bagi menjalankan kajian ini, permodelan homologi untuk T1R2 dan T1R3 telah dijalankan untuk menjangkakan struktur tersebut. Kajian pendokkan protein-protein telah dijalankan antara neokulin dan T1R2 serta T1R3, yang menunjukkan terdapat hubungan yang kuat dengan penemuan kajian sebelumnya mengenai sisa penting neokulin dan bagaimana ia berinteraksi bersama domain ATD kepada T1R3. Sisa tersebut adalah His11, Asp91, Tyr21, Asn44, Arg48, Tyr 65, Val72 dan Phe94. Kompleks dok terbaik itu kemudiannya diuji kepada simulasi dinamik molekul untuk analisis lanjutan. Hasil simulasi dinamik molekul menunjukkan sumbangan daripada sisa penting neokulin dalam membentuk ikatan hidrogen dengan sisa reseptor. Tenaga yang mengikat antara Neokulin dan setiap T1R2 dan T1R3 juga turut dihitung. Keputusan ini menyimpulkan bahawa rasa manis neokulin dan kebolehan mengubah suai adalah aktif hanya apabila ia mengikat kepada domain terminal amino T1R3.

Kata kunci: Neokulin; pemodelan homologi; pendokkan protein-protein; simulasi molekul dinamik; T1R2\T1R3

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*Pengarang untuk surat-menyurat; email: r-bahiah@utm.my