It might be that your PHP script is leaking.
Make sure you have mysql_close() around the place. Also why is your MaxClients so insanely high? Unless you are running very, very, popular websites I dont think you need MaxClients 1000. Also You want MySQL to eat up ram, if set up properly. So it works off RAM more than your hard drive.
To be perfectly honest it looks like you need someone to optimize your server for you. But first make sure your php scripts are running mysql_close(). See if that helps.