Yes, the first thing is to make sure that you eliminate movement blur. So putting the camera/lens on a tripod and using a remote, can mostly stop camera movement, but you'll need a faster shutter speed if you're shooting hand held or if your subject is moving.
The rule of thumb for shooting hand held, is that you want 1/focal length. So shoot for a shutter speed of 1/300. Some say that you should take the crop factor into account, which makes it 1/480 (1/500).
As you will see, you need a lot of light to get shutter speeds like that, with a lens like that. You will likely need to crank up the ISO.
Once you are sure that you can control motion blur, then look at which apertures will give you the best image quality. As mentioned, it's probably around F8 to F11.
Also, lenses like this tend to be worse at the ends of their zoom range. So shooting at 200-250mm will probably get you a sharper photo than shooting at 300mm.