The link between the structural change of a molecule and its function is of fundamental importance since it provides direct insight into the mechanism of complex biological processes. Recent years have witnessed noticeable advances in the analysis of complex molecular conformations, however, the understanding of their conformational dynamics remains a formidable challenge and revolutionary advances are still demanded in the analysis of the chemical composition and structure of biomolecules. The understanding of their conformational dynamics remains a formidable challenge, and revolutionary advances are still demanded. Molecular machines, such as the DNA itself, which work at the core of many cellular activities, are able to modify its conformation and transduce the signal upon binding to specific proteins. In this project, we will develop a DNA-nanotrasducer for real-time detection of conformational changes and the analysis of molecular dynamics as it occurs in-vivo biological processes. iSenseDNA project (https://www.isensedna.eu/), funded by EU in the framework of the EIC-pathfinder open call, aims to provide: (i) the development of DNA-nanotransducers that can perform both detection and conformational analysis of molecular dynamics in one functional unit (ii), Use of bioinformatics approaches to predict the 3D structure of conformational states modeling real-time evolution of interacting DNA-NT and proteins, and machine learning (ML) models to directly link the atomistic structure, conformational state, and dynamics (iii) Assess protein-DNA-NT binding by experimental approaches using linear and “on-chip” non-linear spectroscopies for the detection of vibrational signatures of organic molecular systems, to recognize consequent structural changes in the optical signal in real-time, (iv) Describe DNA-NT/protein interactions at the cellular level and 3D analysis of DNA-NT and model proteins, towards drug discovery. These research efforts will provide a foundation for the next generation of DNA-nanotransducers to be used for high-throughput functional molecular structural detection.