Atom probe tomography: Computational challenges and perspectives

A novel procedure for the application of atom probe tomography (APT) to the structural analysis of biological systems has been recently proposed, whereby the specimen is embedded by a silica matrix and ablated by a pulsed laser source. Based on this technique, our group at the University of Trento is actively collaborating to the efforts of a recently funded EIC-pathfinder consortium, named MIMOSA, whose ultimate goal is to provide an alternative to 4D microscopy with a disruptive technology enabling a high spatial resolution and a chemical sensitivity analysis of biosamples. However, this technique poses several challenges that can be tackled only by a close interplay between the experimental and the modelling/computational efforts. For instance, APT requires that the silica primer be properly inert and bio-compatible, keeping the native structural features of the system at hand while condensing into an amorphous, glassy like coating. We have proposed a molecular dynamics protocol aimed at depicting and characterizing the earliest stages of the embedding process of small biomolecules in a solution of water and orthosilicic acid, here taken as a precursor of the silica matrix. In this first preliminary step, we observe a negligible influence of orthosilicic acid on the behavior of stable folded systems (such as ubiquitin and GFP), while it affects the fluctuations of intrinsically disordered and unstable peptides. However, the entire project presents several challenges that can be tackled (or at least addressed) with the available computational techniques, whether classical or ab initio. I will present our most recent applications in this direction and offer some perspectives for discussion.