Molecular modeling, mutational analysis and conformational switching in IL27: An in silico structural insight towards...

The advancement in proteomics and bioinformatics provokes to discern the molecular-level probe for HIV inhibitor; human interleukin-27 (IL27). Documentation documents that tyrosine residues in IL27 play a pivotal role for interacting with HIV, causing apoptosis of the HIV+ cells. Primarily, 3D structure of human wild-type (WT) IL27 was built through manifold molecular modeling techniques after the satisfaction of stereo-chemical properties. Its essential tyrosine residues were identified. Two mutant models for IL27 were prepared following the similar protocol by first substituting the tyrosine residues with glycine (MT_G) and then with alanine (MT_A) in the WT protein. Molecular dynamics (MD) simulation was performed to obtain a stable conformation. Conformational alterations in WT, MT_G and MT_A (before and after MD simulation) disclosed that MT_A was the steadiest one with the best secondary structure conformation supported by statistical significances. Though huge RMSD variations were observed on superimposing the MT structures on WT individually, the MTs were examined to share similar SCOP/CATH fold with TM-score=0.8, indicating that they retained their functionality even after mutation. Electrostatic surface potential again unveiled MT_A to be the most stable one. MT_A was thereby revealed to be the potent peptide inhibitor for HIV. This probe presents a pathway to investigate and compare the bio-molecular interaction of WT IL27 and MT_A IL27 (strongest model) with HIV in the future. This is the first report regarding the structural biology of IL27 accompanied by alteration at its genetic level and delving into the unknown residue-level and functional biochemistry for bringing about an annihilation towards AIDS.