Graphene quantum dots (GQDs) have attracted significant attention in biomedicine, while extensive investigations have revealed a reverse regarding the potential biotoxicity of GQDs. In order to supplementing the understanding of the toxicity profile of GQDs, this study employs a molecular dynamics (MD) simulation approach to systematically investigate the potential toxicity of both GQDs and Graphene Oxide Quantum Dots (GOQDs) on the Anterior Gradient Homolog 2 (AGR2) protein, a key protein capable of protecting the intestine. We construct two typical simulation systems, in which an AGR2 protein is encircled by either GQDs or GOQDs. The MD results demonstrate that both GQDs and GOQDs can directly make contact with and even cover the active site (specifically, the Cys81 amino acid) of the AGR2 protein. This suggests that GQDs and GOQDs have the capability to inhibit or interfere with the normal biological interaction of the AGR2 active site with its target protein. Thus, GQDs and GOQDs exhibit potential detrimental effects on the AGR2 protein. Detailed analyses reveal that GQDs adhere to the Cys81 residue due to van der Waals (vdW) interaction forces, whereas GOQDs attach to the Cys81 residue through a combination of vdW (primary) and Coulomb (secondary) interactions. Furthermore, GQDs aggregation typically adsorb onto the AGR2 active site, while GOQDs adsorb to the active site of AGR2 one by one. Consequently, these findings shed new light on the potential adverse impact of GQDs and GOQDs on the AGR2 protein via directly covering the active site of AGR2, providing valuable molecular insights for the toxicity profile of GQD nanomaterials.

石墨烯量子点（GQD）在生物医学领域引起了极大的关注，而广泛的研究揭示了 GQD 潜在生物毒性的相反情况。为了补充对GQD毒性特征的理解，本研究采用分子动力学（MD）模拟方法系统研究GQD和氧化石墨烯量子点（GOQD）对前梯度同系物2（AGR2）的潜在毒性蛋白质，一种能够保护肠道的关键蛋白质。我们构建了两个典型的模拟系统，其中 AGR2 蛋白被 GQD 或 GOQD 包围。 MD结果表明GQD和GOQD都可以直接接触甚至覆盖AGR2蛋白的活性位点（具体为Cys81氨基酸）。这表明GQD和GOQD具有抑制或干扰AGR2活性位点与其靶蛋白正常生物相互作用的能力。因此，GQD 和 GOQD 对 AGR2 蛋白表现出潜在的有害影响。详细分析表明，GQD 由于范德华 (vdW) 相互作用力而粘附在 Cys81 残基上，而 GOQD 通过 vdW（初级）和库仑（次级）相互作用的组合粘附在 Cys81 残基上。此外，GQDs聚集体通常吸附在AGR2活性位点上，而GOQDs则一一吸附在AGR2活性位点上。因此，这些发现为 GQD 和 GOQD 通过直接覆盖 AGR2 的活性位点对 AGR2 蛋白的潜在不利影响提供了新的线索，为 GQD 纳米材料的毒性特征提供了有价值的分子见解。