bro i think the BEST route is:
ISB - LHR= motorway
LHR- RYK=N5 (stay at RYK)
RYK- KHI=N5
some good hotels in RYK:HOTEL LAMIS,HOTEL WHITE PALACE AND AL-MASHRIQ HOTEL(I GUESS)
my suggestion of staying in RYK is,you will probably reach there at sunset (IA) and if u go further thn after sadiqabad,following the N5 route,there is some portion of N5(sadiqabad-sukkur) which is so rough to drive at night.that would bother u much..
and if you go via "fsd-shorkot-kabirwala-multan" that would be shorter undoubtedly but besides the fact tht it's a single road(that would take even more tym than that of N5) the road condition isnt too good to drive..
so i would suggest you to go via N5
hav a safe journey.. 