Topological Data Analysis Gives Two Folding Paths in HP35(nle-nle), Double Mutant of Villin Headpiece Subdomain

The folding dynamics of proteins is a primary area of interest in protein science. We carried out topological data analysis (TDA) of the folding process of HP35(nle-nle), double-mutant of villin headpiece subdomain. Using persistent homology and non-negative matrix factorization, we reduced the dimension of protein structure into two, and investigate the flow in the reduced space. We found this protein has two folding paths, distinguished by the pairings of inter-helix residues. Our analysis showed the excellent performance of TDA in capturing the formation of tertiary structure.

Structural Consequences of the Villin Headpiece Interaction with a Carbon Nitride Polyaniline (C3N) Nanosheet

ABSTRACTCarbon nitride polyaniline (C3N) nanosheets shared a similar structure with graphene and have been utilized in biomedical applications since its recent successful synthesis. However, limited information was known about the interaction of this next-generation nanomaterial with biomolecules, which might hamper its applications in living tissues. Here, by using all-atom molecular dynamics (MD) simulations, we investigated the interaction between a C3N nanosheet and the prototypical protein villin headpiece (HP35), in order to identify the mechanistic determinants of such interaction; this knowledge will provide guidelines about C3N’s biocompatibility. Our MD simulations revealed that the C3N-based nanomaterial caused the partial denaturation of HP35 once the protein was bound on its surface. That is, upon adsorption, we observed the loss of the protein’s interior hydrogen bonds and the native contacts, which were related with unwinding events in the protein’s helices. The protein/C3N nanosheet interacting process was dominated by vdW contributions to the energy and the stepwise changes observed in the values of this energy term suggested a gradual unfolding pattern of HP35 during the absorption event. Furthermore, we also found that the interaction energy showed a linear correlation with the native Q ratio of HP35, suggesting that the degree of HP35 unfolding was linearly time-dependent to the interaction energy. Our findings shed light on the underlying molecular mechanism of the potential consequences of C3N-based nanostructures to proteins, which might delineate the future applications of these nanomaterials in biomedicine.