iterating over files

[buran]

something like this

names = ['ligand1.inp','ligand2.inp','ligand3.inp','ligand4.inp']
for i, name in enumerate(names, start=1):
    with open('CONFIG.inp') as cf, open(f'COFIG{i}.inp', 'w') as f:
        for j, line in enumerate(cf, start=1):
            if j == 3:
                line = line.replace('ligand.inp', name)
            f.write(line)

if you show what ligand names look like it may be possible to avoid explicit list of names. Although your approach - reading the full file in memory then replace ligand.inp is perfectly OK if you are sure there is only one occurrence of ligand.inp in the file, I preferred to make sure the replacement is only in line 3.

Also note I don't know if there is better approach from business point of view to achieve your ultimate goal. My example is what you asked for - create multiple config files