Malaysian Journal of Analytical Sciences Vol 20 No 6 (2016): 1269 - 1277

DOI: http://dx.doi.org/10.17576/mjas-2016-2006-05

 

 

 

IN-SILICO IDENTIFICATION OF POTENTIAL PROTEIN ARGININE DEIMINASE IV (PAD4) INHIBITORS

 

(Pengenalpastian In-Silico yang Berpotensi Sebagai Perencat Protein Arginin Deiminase IV (PAD4))

 

Zalikha Ibrahim^1,4, Bimo Ario Tejo², Muhammad Alif Mohammad Latif¹, Roghayeh Abedi Karjiban¹,

Abu Bakar Salleh³, Mohd Basyaruddin Abdul Rahman^1,3*

 

¹Macromolecular Simulation Laboratory, Department of Chemistry, Faculty of Science,

Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

²Faculty of Applied Science,

UCSI University, No. 1, Jalan Menara Gading, UCSI Heights, 56000 Cheras, Kuala Lumpur, Malaysia

³Enzyme Microbial and Technology (EMTech),

Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.

⁴Department of Pharmaceutical Chemistry, Kulliyyah of Pharmacy,

International Islamic University Malaysia, Bandar Indera Mahkota Campus, 25200 Kuantan, Pahang, Malaysia

 

*Corresponding author: basya@upm.edu.my

 

 

Received: 17 August 2015; Accepted: 3 July 2016

 

 

Abstract

Protein Arginine Deiminase IV (PAD4) is a promising target for treating rheumatoid arthritis. Here, an in-silico screening was performed using PAD4 crystal structure against National Cancer Institute Diversity Set III compounds. Results obtained from the docking studies showed that the compounds have high affinity towards the protein. Visual inspections of the top compounds indicated that they preferred to bind at the front door of the catalytic pocket instead of the back door. The current results from this screening could provide a basis for the development of new PAD4 inhibitors.

 

Keywords: Protein arginine deiminase IV, PAD4, virtual screening, NCI diversity set, structure-based

 

Abstrak

Protin arginina deiminase IV (PAD4) adalah sasaran yang berharapan untuk merawat artritis reumatoid. Di sini, satu saringan in-silico telah dilakukan menggunakan struktur kristal PAD4 terhadap molekul dari Set Beraneka Institut Kanser Nasional III. Keputusan dari pengdokan molekular menunjukkan molekul-molekul tersebut mempunyai daya tarikan yang tinggi terhadap protin. Pemeriksaan secara visual ke atas molekul teratas menunjukkan mereka mempunyai kecenderungan untuk terikat di pintu hadapan poket katalisis daripada di pintu belakang. Keputusan daripada pencarian ini boleh menjadi asas kepada penemuan perencat PAD4 yang baru.

 

Kata kunci: Protin arginina deiminase IV, PAD4, pencarian maya, set beraneka NCI, struktur berasas

 

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