Adaptive Lambda\nScheduling: A Method for Computational\nEfficiency in Free Energy Perturbation Simulations

Recent increases in the availability of computational\npower have\nimproved the accessibility of ligand–protein relative binding\nfree energy (RBFE) calculations; however, these calculations remain\nresource-intensive, which can limit their practical application. RBFE\ncalculations typically use a set of thermodynamic intermediates mediated\nby the transformation coordinate λ. Optimizing λ offers\na way to tune the computational efforts required for a given RBFE\ncalculation. Here, we present Adaptive Lambda Scheduling (ALS), a\nstreamlined approach for on-the-fly bespoke λ scheduling. We\nshow it can achieve substantial reductions in computational cost while\nretaining predictive performance.