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Nanomaterial Functionalization Modulates Hard Protein Corona Formation: Atomistic Simulations Applied to Graphitic Materials

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
Article number2101236
Number of pages1
Journaladvanced materials interfaces
Issue number1
Early online date21 Nov 2021
Accepted/In press2021
E-pub ahead of print21 Nov 2021
Published5 Jan 2022

Bibliographical note

Funding Information: The authors acknowledge Kuo‐Ching Mei for helpful discussions. This work was supported by the BBSRC (grant BB/M009513/1) and EPSRC (grant EP/N509498/1). Via the membership of the UK's HEC Materials Chemistry Consortium, which is funded by the EPSRC (EP/L000202, EP/R029431), this work made use of the ARCHER2 UK National Supercomputing Service ( ). This work was supported by The Alan Turing Institute under EPSRC grant EP/N510129/1, through the use of time on Tier 2 HPC facility JADE. Publisher Copyright: © 2021 The Authors. Advanced Materials Interfaces published by Wiley-VCH GmbH

King's Authors


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 β-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.

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