This is exactly the opposite argument I'd make from entropy:
https://www.npr.org/sections/bryantpark/2008/01/knot_theory_...
There's many ways that a string can be knotted and only one way it can not be knotted.
the argument is that the folding process would require the protein to go through an intermediate: forming a loop and then getting one end to go through the loop requires a very specific set of conformations, and reducing the number of conformations has an "entropic cost". Note also that the final post-folding form of a knotted protein isn't really a continuum of many different conformations, but probably one "locked" one which means there really is only a small set of conformations the protein can adopt once locked into the folded, knotted state.
In protein folding, there is not "only one way it can not be knotted"; you have to include all the degrees of freedom in the backbone available in the unfolded state (I am ignoring hydrophobicity and other important sources of entropy which help proteins fold rapidly to the "correct" final state). We already know this pretty well from more basic polymer physics,
but, entropy being subtle, I'm sure there are many different forces at play.
So there are tons of folding configurations, and entering a knotted state restricts a lot of the freedom-to-fold a protein would have