Computation driven development of novel vivo-like-DNA-nanotransducers for biomolecules structure identification

Introduction

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.

Challenges in Understanding Conformational Dynamics

However, the understanding of their conformational dynamics remains a formidable challenge, and revolutionary advances are still demanded. Molecular machines, such as DNA itself, work at the core of many cellular activities. DNA is able to modify its conformation and transduce signals upon binding to specific proteins.

Project Overview

In this project, we will develop a DNA-nanotransducer for real-time detection of conformational changes and the analysis of molecular dynamics as they occur in in-vivo biological processes.

Project Aims

The project aims to provide:

1. The development of DNA-nanotransducers that can perform both detection and conformational analysis of molecular dynamics in one functional unit.
2. Use bioinformatics approaches to predict the 3D structure of conformational states, modeling real-time evolution of interacting DNA-nanotransducers (DNA-NT) and proteins, and machine learning (ML) models to directly link the atomistic structure, conformational state, and dynamics.
3. 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.
4. Describe DNA-NT/protein interactions at the cellular level and conduct 3D analysis of DNA-NT and model proteins, towards drug discovery.

Conclusion

These research efforts will provide a foundation for the next generation of DNA-nanotransducers to be used for high-throughput functional molecular structure.