Bridging Experiments and Simulations to Address Computational Challenges in Atom Probe Tomography and Structural Biology

This thesis investigates the fundamental mechanisms governing the application of an experimental technique, Atom Probe Tomography (APT) to the field of structural biology through a combination of atomistic simulations and theoretical modeling. In fact, APT typically is utilized to determine the properties of metals and alloys, but recently has got a huge leap forward towards new fields of application, among these, the protein structure determination field. Thus, the primary objective of this manuscript is to improve the reliability and interpretability of APT analyses by flanking the experimental findings with theoretical calculations, providing a predictive framework to rationalize the APT workflow at the nanoscale. A first part of the work focuses on the interaction between silica and biomolecular systems. Using classical molecular dynamics simulations, structural and dynamical properties of these hybrid interfaces are characterized, highlighting how adsorption phenomena influence the local protein behavior, with consequences on the dynamics of biomolecular features. These results provide insight into the challenges of analyzing organic–inorganic systems with APT. The study then focuses on the evaporation mechanisms of cations from non-conductive nanosamples under the influence of ultrafast terahertz pulses. By employing ab initio molecular dynamics simulations, this work highlights the role of transient electric/laser fields in triggering field evaporation, offering a possible framework to better understand experimental observations and to extend APT applicability to insulating materials. A further contribution of this thesis lies in the investigation of defects in sol–gel silica and their impact on APT analysis. Through computational analysis concerning Density Functional Theory calculations, it is proposed that structural impurities significantly improve the conductivity of the APT silica specimen, underlining the importance of accounting for material imperfections when trying to develop a framework to analyze insulators like silica within the APT workflow. Overall, this thesis aims at bridging theoretical calculations and experimental findings, elucidating the key role that in silico methods might play as complementary techniques to provide predictive insights into the main procedures, phases and processes of APT. The findings presented here help to advance the understanding of APT in challenging new frontiers and open novel perspectives for its application to structural biology.