期刊
ADVANCED MATERIALS INTERFACES
卷 9, 期 1, 页码 -出版社
WILEY
DOI: 10.1002/admi.202101236
关键词
bio-nano interface; graphene oxide; molecular dynamics simulations; protein corona; point of care
资金
- BBSRC [BB/M009513/1]
- EPSRC [EP/L000202, EP/R029431, EP/N509498/1]
- Alan Turing Institute under EPSRC [EP/N510129/1]
- BBSRC [BB/M009513/1] Funding Source: UKRI
- EPSRC [EP/N510129/1] Funding Source: UKRI
This study used molecular dynamics simulations to investigate the effect of graphene oxide on the adsorption of apolipoprotein-cIII. It was found that apo-c3 is denatured by adsorption to GO due to electrostatic interactions, while it largely retains its tertiary structure when adsorbed to C2GO.
The protein corona is an obstacle to exploiting exotic properties of nanomaterials in clinical and biotechnological settings. The atomic-scale dynamic formation of the protein corona at the bio-nano interface is impenetrable using conventional experimental techniques. Here, molecular dynamics simulations are used to study the effect of graphene-oxide (GO) functionalization on apolipoprotein-cIII (apo-c3) adsorption. An analysis pipeline is developed, encompassing binding energy calculations to protein structure analyses employing uniform manifold approximation and projection (UMAP) dimensionality reduction and clustering. It is found that apo-c3 is denatured by GO adsorption, driven by the large energetic contributions of electrostatic interactions; enthalpic contributions of such binding events outweigh the intraprotein bond enthalpy required to maintain the protein tertiary structure. Through denaturing and exposing buried hydrophobic residues, the protein backbone is stabilized by forming beta-bridges, which serve as binding motifs for protein-protein interactions that drive further protein aggregation on the nanomaterial surface. In contrast, adsorption on double-clickable azide- and alkyne-double functionalized GO (C2GO), apo-c3 largely retains its tertiary structure. Binding with the nanomaterial surface is dominated by weaker van der Waals interactions that are dispersed over the protein surface, where charged protein residues are sterically hindered by azide functional groups. The apo-c3 C-terminus remains unchanged upon C2GO adsorption, conserving its lipid-binding function.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据