Genomics & Informatics

Korea Genome Organization (한국유전체학회)
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M Protein from Dengue virus oligomerizes to pentameric channel protein: in silico analysis study

  • Ayesha Zeba (Department of Life Sciences, Bangalore University) ;
  • Kanagaraj Sekar (Laboratory for Structural Biology and Bio-computing, Computational and Data Sciences, Indian Institute of Science) ;
  • Anjali Ganjiwale (Department of Life Sciences, Bangalore University)
  • Received : 2023.04.25
  • Accepted : 2023.07.11
  • Published : 2023.09.30
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Abstract

The Dengue virus M protein is a 75 amino acid polypeptide with two helical transmembranes (TM). The TM domain oligomerizes to form an ion channel, facilitating viral release from the host cells. The M protein has a critical role in the virus entry and life cycle, making it a potent drug target. The oligomerization of the monomeric protein was studied using ab initio modeling and molecular dynamics simulation in an implicit membrane environment. The representative structures obtained showed pentamer as the most stable oligomeric state, resembling an ion channel. Glutamic acid, threonine, serine, tryptophan, alanine, isoleucine form the pore-lining residues of the pentameric channel, conferring an overall negative charge to the channel with approximate length of 51.9 Å. Residue interaction analysis for M protein shows that Ala94, Leu95, Ser112, Glu124, and Phe155 are the central hub residues representing the physicochemical interactions between domains. The virtual screening with 165 different ion channel inhibitors from the ion channel library shows monovalent ion channel blockers, namely lumacaftor, glipizide, gliquidone, glisoxepide, and azelnidipine to be the inhibitors with high docking scores. Understanding the three-dimensional structure of M protein will help design therapeutics and vaccines for Dengue infection.

Keywords

Acknowledgement

Anjali Ganjiwale acknowledges research funding from SERB, Department of Science and Technology (DST-TARE) grant, TAR/2022/000483, Govt. of India. Ayesha Zeba acknowledges fellowship support from Minority Welfare Department, Govt. of Karnataka, India.

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