Computational platform for designing novel herbicides targeting plant g-quadruplex DNA structures

Overview

This project proposes a computational platform for designing novel herbicides by targeting G-quadruplex (G4) DNA structures in plants. G-quadruplexes are four-stranded helical DNA folding motifs that regulate multiple biological processes and have been identified as a ubiquitous regulatory element in plants. By applying molecular dynamics (MD) simulations and free-energy calculations to study drug binding modes on these structures, the platform aims to identify compounds with new modes of action, offering improved efficiency, selectivity, and non-toxicity compared to existing herbicides.

Technical specifications

Key features:

• Molecular dynamics simulations focused on process free energies to benchmark drug specificity
• Computational predictions validated against experimental FRET data, achieving agreement within 5 percent
• Identification of competitive binding poses to deepen understanding of drug-DNA interactions
• In vitro toxicity assessment integrated with computational screening via feedback loops
• Digital and AI layer to incorporate toxicity data from experiments and databases into screening
• Capability to include metals or specific functional groups in compound design
• Large-database scanning and systematic MD-based free-energy calculations
• Machine learning and AI frameworks tailored to herbicide-specific properties

Technology readiness level

The underlying computational methodology has been validated through benchmarking against experimental FRET data for metallorganic cancer drug compounds, with predictions within 5 percent of measured values. The approach is now being extended from cancer drug applications to plant biology, requiring approximately one year of further development. Future work includes mapping the spectrum of G4 structures relevant in plants, integrating AI-driven toxicity prediction, and validating candidate herbicides experimentally. The team is seeking partners with herbicidal expertise, equipment support, and key personnel to advance the platform toward maturity.