Protect at high volume

No such thing as too much power unless you have a faulty alternator/voltage regulator.
The hundred amp fuse at the battery is better than none but I would replace it with a 50 Amp, that fuse is really only protecting the power wire from grounding out and burning.

The gains are irrelevant, all they do is attenuate the input.
Set them so you cant hear any amp hiss or noise on quiet passages of music or between tracks.

Make sure your not starving the amp for power. Start at the battery connections and work your way back to the amp, inspect all connections for corrosion and make sure they are tight.
Check the ground wire . It is just as important as the power wire!! Try to ground it as close to the amp as practical, scrape off the paint down to the metal use a oversize screw with a star lock washer and a ring terminal.
Make sure that your power wire and ground are at least 8 gauge.

Next on the list is your speakers and related wiring, check to make sure that your impedence is not too low for the amps rating. and that the wiring is correct and at least 16 gauge, 12 is better.
. You can check the speakers impedance with a Ohmmeter, it wont be exact but it should be close +/- .5 Ohm If you are bridging, make sure the speakers are wired in parallel + with+ and - with - .check the amps rating and bridging configuration, it's normally left positive, right negative, but check!

Having done all the above, and you still have a problem only two possibility's left, Defective speakers or the amp. Check with a qualified installer, buy him lunch, you'll get good advice forever.
I hope it helps. Regards Paul