Molecular Dynamics Simulations Reveal Orientation-Dependent Nanotoxicity of Black Phosphorene toward Dimeric Proteins

Abstract

Phosphorene, a monolayer of elemental phosphorus, has emerged as one of the most significant two-dimensional (2D) atomic crystals in the post-graphene era, as a potential candidate for semiconductor industry, nanotechnology, optoelectronics, and nanomedicine. However, the toxicological effects of this material toward different biomolecules remain elusive. In this article, we perform all-atom molecular dynamics simulations to decipher the effect of interaction and adsorption of two dimeric proteins, namely the HIV-1 integrase and the λ6–85 repressor protein on black phosphorene (BPn). It is revealed that upon purely noncovalent adsorption “on the top” of the BPn surface, the secondary structure of the proteins remains conserved, maintaining all the inter- and intraresidue interactions. In addition, the dimeric structure of the proteins does not dissociate into individual monomeric units, thereby inflicting insignificant to no nanotoxicity. However, if the protein–nanomaterial interaction occurs from an orientation where the edge of the 2D material is directed toward the dimer interface and the axis of dimerization of the protein is perpendicular to the plane of the material, a “clean cut” of the dimer is highly probable, wherein individual monomers are structurally not perturbed. The process of BPn edge-induced dimer cleavage is highly favorable as the Gibbs free energy change accompanying the process is negative for both of the dimeric proteins. Thus, BPn is expected to show orientation-dependent nanotoxicity toward dimeric proteins. For monomeric proteins, however, the extent of nanotoxicity would be significantly milder, and the 2D material may be used as a “molecular scissor” for the nondisruptive cleavage of dimeric proteins.