Mapping the morphological identifiers of distinct conformations via the protein translocation current in nanopores.

Conformational changes of proteins play a vital role in implementing their functions and revealing the underlying mechanisms in various biological processes. It is still challenging to monitor protein conformations with temporal fingerprints of current-resistance pulses in the nanopore technique. Here the low-resolution morphologies of different conformations of a typical integrin, αxβ2, were estimated via relative blockade currents simulated from all-atom molecular dynamics (MD). Distinct conformational states of αxβ2 were directly explained by the volume and shape identifiers. Protein modulation in ionic current was analyzed from the conductivity distribution inside the protein-blocked nanopore. Combining a discrete model with spheroidal approximation, a MD-based approach was developed to theoretically predict the volume and shape of the nanopore for sensing αxβ2. This method was also applicable in specifying morphological identifiers of six other proteins, and the theoretical predictions are in good agreement with the experimental measurements. These results potentiated the validity of this method for the conformational identification of proteins in nanopores.