Title: Residue interaction network analysis and molecular dynamics simulation of 6K viroporin: Chikungunya virus channel proteins

Authors: Chaitra Mallasandra Krishnappa; Pratishtha Rai; Ayesha Zeba; Anjali Ganjiwale

Addresses: Department of Life Science, Bangalore University, Bangalore, 560056, India ' The UT MD Anderson Cancer Center, Houston, Texas, 77030, USA ' Department of Life Science, Bangalore University, Bangalore, 560056, India ' Department of Life Science, Bangalore University, Bangalore, 560056, India

Abstract: 6K of Chikungunya virus are small hydrophobic proteins composed of 61 amino acids classified as a class IIA viroporins. The molecular insights on the structure and membrane interaction of 6K protein are not known. Elucidation of structure and role of 6K protein is an important step to understand and combat Chikungunya infections. The aim of this study is to characterise stable higher order oligomers forming the functional unit of 6K viroporin. Molecular dynamics simulation in dipalmitoylphosphatidylcholine (DPPC) bilayer of different oligomeric states of 6K model shows hexamer to be the most stable form for 6K protein. The residue centrality analysis for hexamer shows higher Z-score for Tyr 9, Phe 18, Trp 19 and Ile 24 as the hub residues for the residue interaction network (RIN). The models obtained point aromatic pocket formed by Tyr 3, Tyr 9 and Trp 11 towards the N and C-terminal facing endoplasmic reticulum lumen. Our study provides the first step towards understanding the structure and function of 6K viroporins of the Chikungunya virus.

Keywords: ab initio modelling; Chikungunya virus; ion channels; oligomers; 6K viroporin.

DOI: 10.1504/IJCBDD.2023.133857

International Journal of Computational Biology and Drug Design, 2023 Vol.15 No.5, pp.412 - 429

Received: 19 Aug 2022
Accepted: 15 Jan 2023
Published online: 04 Oct 2023 *

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