TABLE 2.

Ligand-surrounding interaction energies from the MD simulations of P1 variants of OMTKY3 free in solution and when bound to elastase

	Elastase-OMTKY3		OMTKY3
P1 residue					*	†
Gly	−69.7	−5.7	−70.1	−3.2	−10.3	−9.8
Ala	−70.1	−9.5	−69.3	−4.9	−12.0	−12.1
Ser	−82.3	−9.3	−84.3	−3.6	−11.5	−10.1
Cys	−78.6	−11.3	−77.4	−5.7	−12.7	−13.2
Val	−67.4	−16.9	−69.6	−8.9	−12.6	−13.6
Thr	−77.3	−14.9	−83.0	−5.6	−12.1	−12.2
Leu	−71.1	−16.9	−71.3	−10.7	−12.4	−13.1
Ile	−68.3	−20.0	−70.4	−10.6	−13.4	−13.8
Met	−72.2	−19.0	−78.0	−10.2	−11.5	−11.9
Asn	−75.7	−18.0	−91.8	−6.5	−8.6	−8.0
Asp0‡	−77.2	−15.3	−85.6	−6.3	−5.2	−5.6
Lys0‡	−74.9	−19.3	−83.3	−9.8	−7.6	−7.5
Gln	−82.6	−18.5	−92.7	−8.2	−10.5	−9.9
Glu0‡	−78.3	−18.3	−86.3	−7.9	−6.8	−6.2
His	−72.0	−22.0	−94.5	−8.9	−6.7	−6.8
Phe	−69.5	−23.4	−74.9	−13.6	−12.3	−8.0
Arg0‡	−85.4	−20.5	−104.7	−7.8	−2.4	−6.1
Tyr	ND	ND	ND	ND	ND	−6.7
Trp	−71.2	−27.2	−83.6	−15.8	−10.2	−5.7

Values are given in kcal/mol.

^*Energies are calculated according to and the error in these values is <1.0 kcal/mol. The coefficients used are from Model A in Table 4.

^†Experimental binding data from Lu et al. (38).

^‡0 indicates neutral side chain. has been corrected with the free energy required to protonate/deprotonate the ionic side chain according to where pH is 8.3 (corresponding to the pH used in the association measurements) and pK_a is 12.5, 10.7, 4.5, and 4.0 for Arg(5.7 kcal/mol), Lys(3.2 kcal/mol), Glu(5.1 kcal/mol), and Asp(5.8 kcal/mol), respectively.