Title:Mutational Impact on the Interaction Between Human IL27 and gp130: In silico Approach for Defending HIV Infection
Volume: 15
Issue: 5
Author(s): Arundhati Banerjee, Rakhi Dasgupta*Sujay Ray*
Affiliation:
- Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, Nadia,India
- Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, Nadia,India
Keywords:
MD simulation, human IL27-gp130 complex, mutation, protein-protein interactions, energy calculation, solvent
accessibility, 3-ten helices with α–helices and biostatistics.
Abstract: 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.
