Advanced MD for Ligand binding - Phil Biggin (University of Oxford, UK)

Advanced MD for Ligand-binding – Successes, Problems and Alternatives Phil Biggin University of Oxford, UK Despite the hype that surrounds AI methods, the state-of-the-art method for the prediction of the affinity of a small molecule for its protein target, remains the thermodynamically rigorous approach of free energy perturbation. This is a generalizable approach that has been demonstrated across a wide range of drug targets. However, there are still some targets that remain problematic and the computational cost prohibits this approach in large virtual screening campaigns. In this talk, I will discuss cases where the performance is very good, but focus on our recent efforts to address some of the more difficult scenarios. I will also discuss strategies to employ if the computational cost is considered too great such as in systems with many degrees of freedom/and or weak affinity, such as transporter proteins, or for larger-scale screening programs.