any lbs you put on the line contribute to your defensive line on inside or outside runs. so even if they are your middle lbs they will contribute to the average of your ends.
to my knowledge corners and ends are the two groups who are rolled against first. if the run makes it past those two units then your coverage backers and safeties' averages get a chance to stop it. i can't tell if the coverage lbs and safeties are treated as one unit during that check, or if they are kept seperate. im sure thats not exactly how it works, but between what ive read in dev chats and what ive seen thats my 2 cents.
in order to consistently shutdown a good outside running team, the key is to have better corners and ends than his tackles. sad but true, a lot like real life. if there is a moderate to severe talent gap in his favor, you have to decide if its better to try for as many points as possible or possession of the ball to keep his offense on the sideline. if you're losing late, blitzes can increase the rate at which they fumble.