Solvent dependency of the free energy landscape of a protein translocating graphene nanopores

The translocation of (bio)polymers through nanometer-sized openings in solid-state materials is a key process that allows us to identify the identity, length, and sequence of the biopolymer. The efficiency and speed of this process, however, are influenced by the local environment and the interatomic interactions among all components: the biopolymer, pore material, and solvent environment. In order to quantify and understand this influence, we perform all-atom molecular dynamics and enhanced sampling, implementing metadynamics. For this, we use a model biomolecule, part of the H4 histone protein, and a two-dimensional graphene nanopore. To assess the translocation process and the underlying free-energy landscape of the protein, we model the process within a simple monovalent solution, as well as in a molecular denaturant. Using different collective variables, we calculate the respective free energy profiles of the protein translocation and analyze the influence of the different solvents. Our results enable a fundamental understanding of biopolymer translocation through material openings and the key energetic components that can be evaluated in order to understand and optimize the process in view of nanopore-based biosensing.