Toons,
All bullets start dropping the second they leave the barrel.
To match the line of sight from the scope the barrel has to be tilted upward to create an arc for the bullet flight.
Each load will have two zero' s. The first one will be at close range like 25 yards where the bullet passes through the line of sight of the scope and will stay above the line of sight of the scope out to roughly 250 yards where it will be at zero again, after that the bullet falls below scope line of sight again and stays there.

From a 25 yard sight in groups will be 4 times bigger at 100 yards roughly.
A 1/2 group at 25 yards could be a 2" group at 100 yards.
After getting close at 25 yards you really have to shoot at 100 yards to sight in your rifle. If you have the space then shoot it at 300 yards and you will be able to figure your trajectory for all points in between and you can get your 400 yard drop figures from a chart. If you know the velocity from a chronograph it helps but with your 100 yard sight in, lets say 3" high, and your 300 yard drop amount, lets say 3" , you can get a pretty good guess at your velocity from the drop chart.

Depending on where you are hunting is how you should sight in your rifle.
For open country where long shots my be required a 250 or 300 yard sight in is ideal. For areas where shorter shots will be the norm then a 150 or 200 yard sight in would probably be better.