Nanoconfinement of Myoglobin and Green Fluorescent Protein in Metal-Organic Frameworks (MOFs): A Molecular Dynamics Study

The chemical and structural diversity, as well as the scope of applications of Metal-organic frameworks (MOF) have expanded over the last decade. In the biomedical domain, they have played a significant role acting as a bio-compatible host platform for delivering cargoes inside cells, including the immobilization of proteins within their pores. The proteins myoglobin and the green fluorescent protein (GFP) have been shown to form inclusion complexes in the isoreticular IRMOF series, i.e., within IRMOF-74-VII-oeg and IRMOF-74-IX, respectively, where -oeg is a short ethylene oxide oligomer. The present work studies these two inclusions using all-atom molecular dynamics simulations. We observe that both these inclusions are mainly governed by van der Waals interactions at the protein-MOF interface. The effect of confinement on myoglobin was found to be larger than that of GFP, due to the relatively smaller size difference between the former and its MOF host. The primary signature of the confinement was observed in the root mean squared fluctuations of the protein sidechains. Although experiments could not succeed in the inclusion of myoglobin in IRMOF-74-VII-hex (where -hex is the hexyl group), our simulations suggest that it could be facilely accommodated in the same, suggesting the possibility of kinetic contributions in the experimental observation. Overall, for both the proteins, the tertiary structures and hydration of the surfaces of the proteins were well maintained inside the MOF channels.