Table 1.

Summary of MD Simulations in Each TRPS‐Substrate Complex With a Single Proton Switching Between Different Functional Groups

Protonation state intermediate	SB	PO	CO	SB_PN/PO_PN	SB_PG/PO_PG
E(Ain)	Forms stable H‐bonds with TRPS. Waters are stable in the binding site.	Fewer waters around the PO, which affects the proton delivery.		H‐bonds between PN and Ser377 are missing. Lys87 side chain rotates.	H‐bonds between PN and Ser377 are missing. Lys87 side chain rotates.
E(A‐A)	Gln114 side chain tends to form H‐bonds with PO.	PG, PN and CO form stable interactions with TRPS.	H‐bonds between CO and Thr110 are missing.	H‐bonds between PN and Ser377 are missing.	Thr190 and Ser235 loop moves. Salt‐bridge (Arg141‐Asp305) cannot be retained.
E(Q)indoline	Gln114 side chain occasionally forms H‐bonds with PO.	PG, PN and CO form stable interactions with TRPS.	H‐bonds between CO and Thr110 remain. Substrate is stable in the binding site.	H‐bonds between PN and Ser377 are missing.
E(Q)2AP	Gln114 side chain occasionally forms H‐bonds with PO.	PG, PN and CO form stable interactions with TRPS.	H‐bonds between CO and Thr110 are missing. Substrate is stable in the binding site.	H‐bonds between PN and Ser377 are missing.