title: Box size effects are negligible for solvation free energies of neutral solutes.
abstract: Hydration free energy calculations in explicit solvent have become an integral part of binding free energy calculations and a valuable test of force fields. Most of these simulations follow the conventional norm of keeping edge length of the periodic solvent box larger than twice the Lennard-Jones (LJ) cutoff distance, with the rationale that this should be sufficient to keep the interactions between copies of the solute to a minimum. However, for charged solutes, hydration free energies can exhibit substantial box size-dependence even at typical box sizes. Here, we examine whether similar size-dependence affects hydration of neutral molecules. Thus, we focused on two strongly polar molecules with large dipole moments, where any size-dependence should be most pronounced, and determined how their hydration free energies vary as a function of simulation box size. In addition to testing a variety of simulation box sizes, we also tested two LJ cut-off distances, 0.65 and 1.0 nm. We show from these simulations that the calculated hydration free energy is independent of the box-size as well as the LJ cut-off distance, suggesting that typical hydration free energy calculations of neutral compounds indeed need not be particularly concerned with finite-size effects as long as standard good practices are followed.
authors: Department of Chemistry, University of New Orleans, 2000 Lakeshore Drive, New Orleans, LA, 70148, USA.
authors: Sreeja
authors: S
authors: Parameswaran
authors: David L
authors: DL
authors: Mobley
mesh_terms: D006863:Hydrogen-Ion Concentration; D047028:Macrocyclic Compounds / Q000737:chemistry*; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D012996:Solutions; D012997:Solvents / Q000737:chemistry*; D055672:Static Electricity; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
chemical_list: D047028:Macrocyclic Compounds; D012996:Solutions; D012997:Solvents; D014867:Water