Relative Binding Free Energy

Alchemical free-energy calculations with OpenFE on OpenMM: relative binding ΔΔG across a network of ligand pairs (hybrid topology, Hamiltonian replica exchange, MBAR), absolute hydration ΔG, and REST2 replica-exchange sampling of a docked complex. Every result carries its uncertainty and convergence checks; under-converged pairs are flagged, not averaged in.
Upload a receptor PDB.
Estimated minimum cost: $—

Calculation

Choose the free-energy or sampling method.

Input

Upload a prepared receptor PDB (with hydrogens) and docked poses as SDF (up to 30 ligands). Ligands are named by their SDF title; the first pose of each name is used.

Receptor PDB
or drop a file here
Docked poses (SDF)
or drop files here

Perturbation network

Pair ligands that share a scaffold. Each pair a → b gives ΔΔG = ΔG(b) − ΔG(a) from a complex and a solvent leg; closed cycles report a cycle-closure residual. Up to 60 pairs. An optional experimental ΔG for one ligand anchors the per-ligand estimates.

Upload at least two ligands to pair them.

Sampling

Hamiltonian replica exchange across the lambda windows, analysed with MBAR. Results report the MBAR (or repeat) uncertainty, forward/backward agreement and window overlap; any failed check marks the result as not converged. One job simulates at most 300 complex-equivalent ns.