Computer aided drug design of modulators of telomeric

Telomeres are specialized nucleoprotein structures that protect chromosome ends and maintain genome stability. Their function is regulated by a network of telomeric proteins, which play critical roles in telomere maintenance, DNA damage response, and cellular senescence. Dysregulation of telomeric proteins is associated with ageing and several cancers, making them promising targets for therapeutic intervention. However, the development of selective small-molecule modulators remains challenging due to the complexity and dynamic nature of telomeric protein interactions.

This PhD project aims to apply computer-aided drug design (CADD) approaches to identify and optimize novel small-molecule modulators of selected telomeric proteins. The research will integrate structural bioinformatics, molecular docking, virtual screening, molecular dynamics simulations, and free-energy calculations to characterize protein–ligand interactions and identify promising chemical scaffolds. Structure-based and ligand-based approaches will be combined to improve binding affinity, selectivity, and physicochemical properties of candidate compounds.

The project will also investigate the conformational dynamics and stability of protein–ligand complexes, providing molecular-level insights into mechanisms of modulation. Computationally prioritized compounds may subsequently serve as candidates for experimental validation. Overall, the research will establish an integrated computational workflow for discovering novel telomeric protein modulators and contribute to a better understanding of telomere biology. The outcomes may support future development of therapeutic strategies targeting telomere-associated mechanisms in cancer and age-related diseases.