Graphene as a potential treatment for acute migraine: A computational study

Abstract

Listen

Translate article

Here, we study the graphene nanosheets with various functional groups including –COOH, -NH2, –COOH-NH2, -OH, and O interacting with calcitonin receptor-like receptor (CLR) in combination with receptor activity-modifying protein (RAMP1). This study uses molecular dynamics (MD) simulations to study the interaction between CLR/RAMP1 and graphene-family planar nanosheets: Gr, Gr-COOH, Gr-NH2, Gr-OH, Gr-O, and Gr-COOH&-NH2. The Ubrogepant was used to validate the results and comparison of the Gr-family performance. The MD simulation data revealed that Gr, Gr-OH, and Gr-COOH interacted with CLR/RAMP1 more intensely, due to changes in electrostatic interactions. Furthermore, the binding affinity of the nanosheets, as well as Ubrogepant toward the protein, have been calculated using docking. Docking analysis with both CLR fragment and CLR/RAMP1revealed similar trends in the interactions where Gr-OH has the strongest affinity in binding to the neuropeptide. The DFT calculations demonstrated a discernible surface polarity hierarchy among the functionalized graphene materials, revealing Gr-O and Gr-OH with the highest surface polarity, followed by Gr-COOH and Gr-NH2, respectively, consistent with our findings. Altogether, our study shows that three candidates; Gr-OH> Gr-COOH> pristine Gr can inhibit CGRPR binding by disrupting the protein’s structure. Significantly, the Gr-family outperformed Ubrogepant as an indicator of its potential anti-migraine applications. The results of this study provide detailed and reliable theoretical guidance for using the graphene family in treating migraine and can assist in the further development of new graphene-based materials.