Hiya,
I'm no officianado but I was just reading another discussion on here where one chap suggested depressing the E string down pickguard side of the bridge, quite firmly to create a change in angle. This sets the string correctly into the saddle and "should" be done every time we change strings or change tuning.
By the way, I have a similar issue with the first string. I always feel like it's sharper sounding and not like the other 3. I play a bit of slap too, I always have to try and stifle pops to make them percussive.