Introduction: With advances in proteomics, it is essential to investigate the molecularlevel participation of IL27 and gp130 to hinder HIV infection. Their interaction causes cell-cycle arrest in HIV+ cells by activating the receptor-associated JAK signaling and causing apoptosis of cancerous cells.
Methodology: The best human wild-type WT_IL27 model was prepared after varied molecular modeling techniques. The vital tyrosine residues in WT_IL27 were identified, mutated and IL27 was re-modeled. Both wild-type and mutant IL27 were docked individually with human gp130 ectodomain complex. Best cluster sized complex was opted and the complexes (WT and MT) were MD (molecular dynamics) simulated. Protein-protein interacting residues, binding patterns, thermodynamic stability, solvent accessibility and many such parameters were evaluated to affirm the stability in the mutant complex. Statistical significances were drawn too.
Result and Discussion: With statistical significances also, the mutant type (MT) IL27 was comprehended as the most stable one. Their functionality remained the same. Ionic interactions were the most dominating ones. Exceptionally several Arg residues from MT_IL27 appeared to play a major role, thereby stabilizing the simulated MT_IL27-gp130 complexes. Manifold energy estimations for the complexes, electrostatic potential and increment in %helices and %β-sheets revealed the simulated MT_IL27-gp130 complex to be more stable. In the MT_complex, residues forming 3-ten helices remained constant with major increase in α–helices. This thereby infers the complex as the steadiest and most interactive one.
Conclusion: The residual exploration with the detailed structural analysis would aid in the effective drug discovery by targeting the drugs at the interacting sites with the specific binding patterns as analyzed from the study. Conformational stability and other several parameters for thermodynamic stability and accomplishment of strong interaction were also explored. Altogether, this probe provides a limelight towards the mutational alterations in WT IL27, which might allow it to act as a strong peptide inhibitor by shielding HIV entry, more potently.