Closing the Loop: A Computational-Experimental Feedback Approach for Predicting Macrocycle Closure

University of Oxford

The drug development process is expensive and time-consuming, with a primary bottleneck being making the drugs in the laboratory. Recent advances in computation and data science show that it is possible to predict the success of chemical reactions, saving time, money, and resources. This potential is especially important for ring-shaped molecules known as macrocycles, which are of particular value as drugs, as they can interact with certain proteins previously thought to be ‘undruggable’. However, predicting the success of the ring-closing step is a notorious challenge.

Aleksy’s project aims to leverage these advances in computation and data science to understand the factors influencing ring closure and develop tools to predict the success of these important reactions. While 67 macrocycles have been approved as medicines such as antibiotics, antivirals, and for cancer treatment, the majority are derived from nature due to the challenges of laboratory synthesis. Aleksy’s predictive tools will combine computation and experiments to predict whether a macrocycle can form, and how best to form it, before attempts are made in the laboratory.

This approach offers a more efficient, cost-effective, and greener method for macrocycle design, opening up a host of new possibilities in relation to their synthesis. Aleksy’s predictive tools will be automated, freely available, and user-friendly, facilitating their adoption by the wider chemistry community. Ultimately, this project could provide a step-change in macrocycle design, enabling the discovery of therapeutic drugs which were previously considered out of reach.


Aleksy graduated with a first class Master’s degree in Chemistry from the University of Oxford, where he is currently undertaking his PhD in Organic Chemistry. This is in active collaboration with MSD as part of the Synthesis for Biology and Medicine program. Alongside his studies, Aleksy is an organic chemistry tutor at the University of Oxford and is actively involved in the start-up scene at the University. Please do not hesitate to contact him if you would like to know more.