Ligand jumping from the box

I have started the MD simulation of a protein ligand interaction for 100ns. first, i created a box for the protein in center then added the ligand molecules and after the neutralization, i saw all of my protein, ligand and water molecules were inside the box but after running the simulation i found that the ligand and water molecules are outside the box only protein is there in the center of the box. please help me how to solve this problem.