Monte Carlo statistical mechanics for peptides, proteins and nucleic acids in solution — and the program that carried free-energy perturbation out of academia and into the pharmaceutical industry.
Derived from BOSS — the same Monte Carlo machinery, reorganised around residues.
MCPRO performs Monte Carlo statistical-mechanics simulations of peptides, proteins and nucleic acids in solution. It is derived from BOSS, and makes extensive use of the concept of residues — which is what lets it treat a whole protein rather than a small molecule in a box.
Its most consequential capability is computing protein–ligand binding free energies by free-energy perturbation. That is the calculation behind every rung of the lead-optimization campaigns on our research page: which analog to synthesize next, decided before anybody makes it.
Free-energy perturbation is now a routine part of pharmaceutical lead optimization.
Described in their own manual as “a simulation package built around the MCPRO program”, giving non-expert users relative binding free energies via FEP theory.
Schrödinger's FEP+ is now used across the pharmaceutical industry for lead optimization.
Work that used the OPLS force fields should cite those separately — see OPLS-AA/M.