Step 1 take ligand pdb with H antechamber -i ligand.pdb -fi pdb -o ligand.prepin -fo prepi -c bcc -s 2 ### This should generate prepin file parmchk -i ligand.prepin -fi prepi -o anp.frcmod -fo frcmod ### This should generate frcmod file tleap -s -f leaprc.ff99SB ### this will open tleap > source leaprc.gaff ### this will load leaprc.gaff force field > loadamberparams ligand.frcmod ### this loads frcmod generated above > loadamberprep ligand.prepin #### this loads prepin generated above > complex = loadpdb complex.pdb ### this loads protein-ligand complex as "complex" unit > charge complex ### this will show charge on system (if -ve add Na+ else add Cl-) > addions complex Na+ 0 ### this will neutralize the system by adding no. of Na+ ions > solvateoct complex TIP3PBOX 8.0 > saveamberparm complex final.prmtop final.inpcrd