Solvation free energy determines the thermostability of molecules in solution. Accurate prediction of solvation free energy from atomistic simulations have great impact on the understanding of many biologically important processes. What makes the simulation of the solvation free energy difficult is that it consists of competing effects from opposing interactions at a molecular level. To accelerate convergence, separations of the competing forces are necessary. Traditionally formulation of solvation free energy separates van der Waals and electrostatics. We find that further separation of the attractive and repulsive forces within the van der Waals interactions is also necessary. Test calculations with constant pressure molecular dynamics (MD) in water show that the seemingly small nonpolar solvation free energy is made up of relatively large unfavorable contribution from repulsive forces and a canceling favorable contribution from the attractive forces. Our results show good agreement with experimental solvation free energies and those of other computational studies. Alternative to the constant pressure simulation with a fluctuating volume, the same results can be generated with fixed volume but fluctuating number of water molecules --- grand canonical ensemble. With the grand canonical Monte Carlo (GCMC) moves on solvent water, we are able to obtain accurate solvation free energy as well. The GCMC/MD method is shown to yielded accurate results for ligand binding in cytochrome p450, in which case water displacement from a confined binding pocket can not be account for in typical MD simulation time.