Insights into the aquaporin 4 of zebrafish (Danio rerio) through evolutionary analysis, molecular modeling and structural dynamics

Abstract Aquaporins (AQPs) constitute a super family of major intrinsic proteins (MIPs) and aquaporin 4 (AQP4) is one of the most popular protein, participating in different types of bio-physiological pathways in animal, plant and even in bacteria. Zebrafish, considered as a novel model organism, possess an Aquaporine 4 protein (zAQP4) that shares a high degree of homology with mammalian orthologs which was mostly found to be express in brain, ovary, testis, and low levels in other tissues. To focus more light on AQP4 medical related therapeutic applications, the structure of zAQP4 as a drug target protein is extremely essential and there is no such structural information available in protein data bank (PDB). Herein, for the first time we generate the 3D structure of zAQP4 was modeled through a Homology modeling approach. The root-mean-square deviation (RMSD) of atomic positions between the generated model structure and human AQP4, revealed 69.2% sequence identity over align region with RMSD value 2.723 A. Structural integrity of the model was assessed using molecular dynamics simulation studies to achieve a better understanding of the progress, structure, and function of AQP4. Finally residual involvements for druggable pocket identification were made and some important residues such as VAL-237, PRO-272, GLN-274, PRO-277, TYR-278, VAL-118, LEU-122 and LEU-126 which shows highest druggability probability (1.0) that can emphasize the importance of aquaporin-4 as a target protein in the field of drug research in near feature.