SEPARATION-SHIFTED SCALING, A NEW SCALING METHOD FOR LENNARD-JONES INTERACTIONS IN THERMODYNAMIC INTEGRATION

A new method of simultaneously scaling and shifting the Lennard-Jones (LJ) potential in molecular dynamics (MD) and thermodynamic integratio n (TI) simulations is presented. The approach allows the smooth creati on or annihilation of atoms or molecules in an ensemble of solvent mol ecules during a molecular simulation. By scaling and shifting the LJ p otential in the direction of the interatomic distance between particle s, the method eliminates the problem of the creation or annihilation o f a large repulsive LJ potential at the initial or final state of a TI . The optimal degree of shifting and scaling the LJ potential as a fun ction of a control variable lambda was studied for the annihilation an d creation of neon in aqueous solution. The method was further tested on the calculation of the free energy of aqueous solvation of a small molecule, ethanol. In contrast to linear scaling of the LJ potential d uring TI, the calculated free energies using the new separation-shifte d scaling approach are reasonably well converged after 200-500 ps of s imulation and show smaller hysteresis comparing forward and reverse TI .