  Although rare, an increasing number of proteins have been observed to contain
entanglements in their native structures. To gain more insight into the
significance of protein knotting, researchers have been investigating protein
knot formation using both experimental and theoretical methods. Motivated by
the hypothesized folding pathway of $\alpha$-haloacid dehalogenase (DehI)
protein, Flapan, He, and Wong proposed a theory of how protein knots form,
which includes existing folding pathways described by Taylor and B\"olinger et
al. as special cases. In their topological descriptions, two loops in an
unknotted open protein chain containing at most two twists each come close
together, and one end of the protein eventually passes through the two loops.
In this paper, we build on Flapan, He, and Wong's theory where we pay attention
to the crossing signs of the threading process and assume that the unknotted
protein chain may arrange itself into a more complicated configuration before
threading occurs. We then apply tangle calculus, originally developed by Ernst
and Sumners to analyze the action of specific proteins on DNA, to give all
possible knots or knotoids that may be discovered in the future according to
our model and give recipes for engineering specific knots in proteins from
simpler pieces. We show why twists knots are the most likely knots to occur in
proteins. We use chirality to show that the most likely knots to occur in
proteins via Taylor's twisted hairpin model are the knots $+3_1$, $4_1$, and
$-5_2$.
