Solvation Free Energy

Alchemical coupling for computing solvation free energy (excess chemical potential) using OpenMM. The molecule is coupled into its environment in two phases: LJ interactions are turned on first using a soft-core potential, then Coulomb interactions are turned on (with LJ fully on).

Lambda Schedule

• Phase 1 (~3/4 of windows): lambda_vdw 0→1 (soft-core), lambda_coul = 0.

• Phase 2 (~1/4 of windows): lambda_coul 0→1, lambda_vdw = 1.

Initial Force Decomposition

system.to_omm_system() produces (bonded forces omitted):

Force	Computes	Per-particle params
NonbondedForce (PME)	Coulomb (real + reciprocal + self)	charge, sigma=1.0, eps=0
NonbondedForce exceptions	1-4 Coulomb + 1-2/1-3 exclusions	chargeProd
CustomNonbondedForce (LJ)	A(type1,type2)*invR6^2 - B(type1,type2)*invR6	type (int)
CustomBondForce (1-4 LJ)	C*eps*((sigma/r)^n - (sigma/r)^m)	eps, sigma, n, m

Final Alchemical Force Table

After modification (M = decoupled molecule, env = everything else):

Force	Scope	Lambda-dependent?
NonbondedForce (PME)	All pairs (unchanged)	M charges × lambda_coul
NonbondedForce exceptions	1-4 Coulomb + exclusions (unchanged)	No
Original CustomNonbondedForce	(env, env) + (M, M)	No
Alchemical CustomNonbondedForce	(M, env) soft-core	lambda_vdw
Correction CustomBondForce	M-M beyond-1-4 pairs	lambda_coul
1-4 CustomBondForce	All 1-4 LJ (unchanged)	No

API Reference

SFEManager(system, mol_id[, n_lambda])

Alchemical system for solvation free energy calculation.