Impact of Graphene and Its Oxides on the Structural and Dynamical Properties of Transforming Growth Factor β3

Through conventional and metadynamics molecular dynamics simulations, this study investigates global adsorption behaviors of the TGF-β3 protein on ultralarge-scale 20 nm × 20 nm PG20nm and GO20nm sheets, along with localized adsorption phenomena on smaller-scale 1.2 nm × 1.6 nm PG1.2nm and GO1.2nm surfaces. Global adsorption results reveal distinct material-dependent preferences: TGF-β3 selectively adsorbs at edge sites of PG20nm sheets, with residue segments Tyr6-Tyr49 and Pro70-Pro76 maintaining close interfacial contact with the planar edges. Conversely, TGF-β3 favors central-domain adsorption on GO20nm sheets, as evidenced by residues Asp3-Arg25, His34-Phe43, and Glu84-Ser112 forming extensive interactions with the central sheet region. The results confirm that both PG20nm and GO20nm sheets effectively adsorb the TGF-β3 protein. Based on the localized adsorption outcomes of four uniformly dimensioned PG1.2nm sheets (1.2 × 1.6 nm) simultaneously interacting with four distinct regions of TGF-β3, the region containing the highest density of aromatic amino acid residues exhibits the strongest adsorption affinity. The GO1.2nm sheet yields consistent adsorption results across the four targeted regions of TGF-β3. However, despite the advantageous positioning of both sheets for localized TGF-β3 adsorption, molecular dynamics simulations reveal that neither sheet maintains conformational consistency between the adsorbed TGF-β3 structures and the native conformation. Notably, root-mean-square fluctuation (RMSF) analysis reveals that only in the global adsorption system (GO20nm/TGF-β3) and the localized adsorption system, where TGF-β3 adsorbs exclusively onto a single GO1.2nm sheet (GO/TGF-β3), does TGF-β3 exhibit the capability to maintain native-like conformational characteristics. This structural preservation facilitates functional retention during adsorption processes, thereby enabling the rational design of novel graphene-based sustained-release delivery platforms.