Collins told CNN's "New Day" that the President may have had the impression it was normal to speak with the FBI chief in private after Comey pulled him aside in January at Trump Tower to discuss an unsubstantiated dossier that contained salacious personal accusations against Trump.
"I wonder if perhaps that made the President think that whenever there is some conversation to be had with the FBI director that it should be one-on-one because he had two subsequent one-on-one meetings as well as other phone calls with the FBI director," Collins said.
"That doesn't make it right, but ironically perhaps the FBI's actions in that first meeting sent a signal to the President that this is how their interactions should take place."
In testimony that rocked Washington, Comey told lawmakers Thursday how Trump had urged him in private to drop the FBI's probe into former national security adviser Michael Flynn. Trump has denied doing so.
Comey said he chose to take detailed notes about his interactions with Trump because of concerns the White House and President would lie about them if he didn't.
Collins suggested Trump's political inexperience may have led him to violate norms and cross boundaries in his first months in Washington.
"This reflects the fact that this is the first President in our history who has had neither a military nor a political background, and I think he just does not fully understand or appreciate the boundaries and that it is totally wrong -- I'll go beyond inappropriate," the senator from Maine said.
"It is wrong for the President of the United States to tell or imply to an FBI director that an investigation should not go forward," she said, describing Comey's testimony to be "credible, candid and thorough."
Collins isn't the first Republican to suggest inexperience may be behind some of Trump's moves.
House Speaker Paul Ryan on Thursday sought to explain Trump's behavior with Comey.
"He's new to government. So he probably wasn't steeped in the long-running protocols that establish the relationships between DOJ (Department of Justice), FBI and White House."
Pushed further by CNN, Ryan said, "I'm not saying it's an acceptable excuse. It's just my observation.
"He's new at government, and so therefore I think that he -- he is learning as he goes."