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. Author manuscript; available in PMC: 2022 Jan 13.
Published in final edited form as: J Chem Theory Comput. 2021 Mar 25;17(4):2541–2555. doi: 10.1021/acs.jctc.0c01305

Table 1.

Summary of Simulation Conditionsa

Condition HIS46 Protonated Ligands (+1 charge) Deprotonated Ligands
(+0 charge)		 Salt Restraint
Potential
Baseline HIP 1C5X, 1C5Y, 1C5Z, 1GI7, 1GJ7, 1GJ8, 1GJA, 1GJB, 1GJD, 1O3P – Counterions 1DOF
Baseline + 150 mM salt HIP 1C5X, 1C5Y, 1C5Z, 1GI7, 1GJ7, 1GJ8, 1GJA, 1GJB, 1GJD, 1O3P – 150 mM 1DOF
Baseline + Deprotonated Ligands HIP 1C5X, 1C5Y, 1C5Z, 1GI7 1GJ7, 1GJ8, 1GJA, 1GJB, 1GJD, 1O3P Counterions 1DOF
All-HIP HIP 1C5X, 1C5Y, 1C5Z, 1GI7 1GJ7, 1GJ8, 1GJA, 1GJB, 1GJD, 1O3P 150 mM 1DOF/6DOF
All-HID HID 1C5X, 1C5Y, 1C5Z, 1GI7, 1GJ7, 1GJ8, 1GJA, 1GJB, 1GJD, 1O3P – 150 mM 1DOF
Small-HIP Mixed 1C5X, 1C5Y, 1C5Z, 1GI7 (HIP)1GJ7, 1GJ8, 1GJA, 1GJB, 1GJD, 1O3P (HID) – 150 mM 1DOF
Small-HID Mixed 1C5X, 1C5Y, 1C5Z, 1GI7 (HID) 1GJ7, 1GJ8, 1GJA, 1GJB, 1GJD, 1O3P (HIP) 150 mM 1DOF
a

The baseline corresponds to a default setup with full ligand and protein protonation, salt concentration at charge neutralizing amount, and 1DOF restraint. Singular condition changes to the baseline: 150 mM salt concentration, and deprotonated ligand phenol. Alternative protonation states are tested with variable ionization at the ligand phenol and His-46 to model the effect of hydrogen bonding potential on binding free energy prediction.