PG20(China Pharmaceutical University)

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 PG_20nm and GO_20nm sheets, along with localized adsorption phenomena on smaller-scale 1.2 nm × 1.6 nm PG_1.2nm and GO_1.2nm surfaces. Global adsorption results reveal distinct material-dependent preferences: TGF-β3 selectively adsorbs at edge sites of PG_20nm 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 GO_20nm 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 PG_20nm and GO_20nm sheets effectively adsorb the TGF-β3 protein. Based on the localized adsorption outcomes of four uniformly dimensioned PG_1.2nm 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 GO_1.2nm 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 (GO_20nm/TGF-β3) and the localized adsorption system, where TGF-β3 adsorbs exclusively onto a single GO_1.2nm 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.