Stabilization of Trp-cage within Confinement by Optimizing the Interface Hydrophobicity

Understanding the interaction between proteins and confining interfaces is a critical step towards revealing the folding behaviors of protein in cellular context. In particular, the hydrophobicity of the confinement is an important factor that may affect the hydrophobic collapsing of the proteins. Hence, to study the hydrophobic effects of the confinement on the protein behaviors, we performed molecular dynamics simulations of Trp-cage miniprotein sandwiched between two graphene sheets with varying hydrophobicity by tuning the interaction potential. The structural variations of the protein was characterized by the average root-mean-square-displacement, the radius of gyration of the backbone, and the mean contact area between individual residues and the confining interfaces. The results revealed that the confinement tends to stabilize the native state of Trp-cage by reducing its configurational entropy. Specifically, two stablization mechanisms were identified. The protein may be stabilized by moderately hydrophobic confinement through gentle adsorption and yet without destroying the hydrophobic core of the Trp-cage, or, by highly hydrophilic confinement via volume exclusion caused by dense water layers.