Table I.

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) can- not 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.