(566i) Pysages: Funnel Restraints for Ligand-Receptor Enhanced Sampling Calculations

The Covid-19 pandemic has underscored the pressing need for new, efficient, and accurate methods that can accelerate drug design and discovery. Molecular dynamics (MD) simulations coupled with enhanced sampling methods provide a detailed understanding of Protein-Ligand (P-L) interactions. In the past, complex restraint potentials have been coupled with the metadynamics enhanced sampling method to create Funnel Metadynamics, which calculates free energies in protein complexes. In this work, we propose the use of funnel-like potentials in combination with an expanded set of enhanced sampling methods beyond the metadynamics family to achieve faster and more efficient sampling of P-L interactions. This approach has the potential to accelerate computer-aided drug design and discovery.