Exploring Protein–Nanoparticle Interactions with Coarse‐Grained Protein Folding Models

Understanding the fundamental biophysics behind protein–nanoparticle (NP) interactions is essential for the design and engineering bio‐NP systems. The authors describe the development of a coarse‐grained protein–NP model that utilizes a structure centric protein model. A key feature of the protein–NP model is the quantitative inclusion of the hydrophobic character of residues in the protein and their interactions with the NP surface. In addition, the curvature of the NP is taken into account, capturing the protein behavior on NPs of different size. The authors evaluate this model by comparison with experimental results for structure and adsorption of a model protein interacting with an NP. It is demonstrated that the simulation results recapitulate the structure of the small α/β protein GB1 on the NP for data from circular dichroism and fluorescence spectroscopy. In addition, the calculated protein adsorption free energy agrees well with the experimental value. The authors predict the dependence of protein folding on the NP size, surface chemistry, and temperature. The model has the potential to guide NP design efforts by predicting protein behavior on NP surfaces with various chemical properties and curvatures. The authors successfullybuild a general model to describe the interactions between protein residues and the nanoparticle (NP). Curvature and hydrophobic effects are accurately captured by this model so that predictions of protein behavior in various protein–NP systems are feasible. Therefore, it is expected that this model will play an important role in NP‐biosensor design.