Table 2.

LRA Contributions (kcal/mol) of the Solvation Free Energies for Different Systems^a

	KE07		R6 3/7 F
	RS	TS	RS	TS
${<U_Q-U_0>}_Q^{W+P}$	−78.8	−55.9	−56.6	−63.0
${<U_Q-U_0>}_0^{W+P}$	−0.2	5.7	12.2	7.8
ΔGsolv	−39.5	−25.1	−22.2	−27.6

	HG3		HG3.3b		HG3.7		HG3.17
	RS	TS	RS	TS	RS	TS	RS	TS
${<U_Q-U_0>}_Q^{W+P}$	−56.7	−35.5	−77.9	−42.2	−50.8	−48.4	−46.9	−48.3
${<U_Q-U_0>}_0^{W+P}$	0.4	−0.1	17.0	4.2	−2.2	−0.3	−11.9	−12.2
ΔGsolv	−28.2	−17.8	−30.5	−19.0	−26.5	−24.4	−29.4	−30.3

^aU_Q and U₀ represent the charged and uncharged states, respectively. W and P represent water and protein, respectively. An important point to note here is that the difference in the K_M values does not reflect the true change in binding energy as a protein residue (ASP/GLU) is part of the substrate. We also like to note that the LRA is much less quantitative that the FEP/US approach, but it still provides reliable qualitative information about the difference between GSD and TSS. Note that that as established in our earlier papers the LRA electrostatic contribution is a very good marker for the magnitude of the GSD and TSS.³⁸