Ducati admits it will arrive at Austin on the back foot following its decision to skip MotoGP's pre-season test at the Texan track.
While Honda and Yamaha's factory riders completed a collective 10 days of running in March, Ducati's sole experience comes via Nicky Hayden's brief run around the circuit on a street bike.
Following the season-opening Qatar Grand Prix, where Andrea Dovizioso and Hayden were seventh and eighth respectively, Ducati team manager Vittoriano Guareschi acknowledged his team faces a difficult weekend.
"Unfortunately, since the Ducati Team didn't test at COTA, we're at a bit of a disadvantage to our competitors," Guareschi said.
"The track [is] completely new for us. Nicky did a sort of shakedown with a Panigale R street bike, and from the way he describes it, it will be quite difficult.
"We'll have dual assignments during the early sessions — we have to find a general set-up and the correct settings for the electronics.
"The weekend is a bit of an unknown for us, but we're optimistic."
Dovizioso, who narrowly missed out on a front-row start in Qatar but then faded in the race, said he expected to start at a disadvantage to his MotoGP rivals.
"I haven't been to the Circuit of the Americas, but from the video it looks like a really big and nice track, and it also looks really difficult," Dovizioso added.
"Unfortunately, we didn't test there like some of the other guys, so it will be a problem for us in the beginning."