Red Hot Chili Peppers' 2012 single from the bands' 10th album I'm With You is in standard tuning (EADGBE) and features funky 16th note patterns from guitarist Josh Klinghoffer.
The track kicks off with this explosive riff, which sets up a feel good vibe and an instantly infectious groove. The riff is based on a Gm7 chord played in 10th position, where the highest note moves up and down by a semitone to create a simple melody.
The hardest aspect of the guitar part is maintaining the timing of the melody while keeping a solid 16th note funk feel. The trick is to make sure that your strumming hand keeps a constant 16th note motion.
The melody is a simple movement of your fretting fingers, which you can practise independently of the strumming to begin with. Also, look ahead to the 15th fret before you move up the neck to maximise your chances of landing on the right note.
Get the sound
A bridge position singlecoil pickup is the obvious choice here. If your guitar has humbuckers, reduce the bass level on your amp and raise the treble. How you play will alter what is otherwise a basic guitar tone.
Adjust the position of your pick: strum by the bridge for a bright, percussive tone; or strum nearer the neck for a softer tone. You can coax more brightness and treble out of your guitar by focusing your pick attack on the higher strings, too.