Time-dependent conformational analysis of ALK5-lumican complex in presence of graphene and graphene oxide employing molecular dynamics and MMPBSA calculation

Abstract

Lumican, an extracellular matrix protein avails wound healing by binding to ALK5 membrane receptor (TGF-beta receptor I). Their interaction enables epithelialization and substantiates rejuvenation of injured tissue. To enrich permanence of ALK5-lumican interaction, we employed graphene and graphene oxide co-factors. Herein, this study explicates concomitancy of graphene and graphene oxide with ALK5-lumican. We performed an in silico approach involving molecular modelling, molecular docking, molecular dynamics for 200 ns, DSSP analysis and MMPBSA calculations. Results of molecular dynamics indicate cofactors influential in altering bioactive site of lumican than ALK5. Similarly, MMPBSA calculations unveiled binding energy of apoenzyme as −108.09 kcal/mol, holoenzyme (G) as −79.20 kcal/mol and holoenzyme (GO) as −114.33 kcal/mol. This concludes graphene oxide lucrative in enhancing binding energy of ALK5-lumican in holoenzyme (GO) via coil formation of Lum C13 domain. In contrast, graphene reduced binding energy of ALK5-lumican in holoenzyme (G) modifying Lum C13 into beta sheets. MMPBSA residual contribution analysis of Lum C13 residues revealed binding energy of −13.9 kcal/mol for apoenzyme, −6.8 kcal/mol for holoenzyme (G) and −19.5 kcal/mol for holoenzyme (GO). This supports coil formation propitious for better ALK5-Lum interaction. Highest SASA energy of −21.05 kcal/mol of holoenzyme (G) assures graphene reasonable for improved ALK5-lumican hydrophobicity. As per the motive of the study, graphene oxide enriches permanence of ALK5-lumican. This provides counsel for plausible exploitation of lumican and graphene oxide as targeted/nano drug delivery system to reinstate acute wounds, chronic wounds, corneal wounds, hypertrophic scars and keloids in near future. Communicated by Ramaswamy H. Sarma