Table IV.

The dependence of the pK_a of E286 in CcO on the method used ^(a)

	ΔGp	ΔΔGw→p	$\mathrm{\Delta }\mathrm{\Delta }{G}_{\mathit{sol},LW}^{w\to p(AH,MW)}$	pKa (4.5+ ΔΔGw→p/1.37)
In water	−79.3	---
In protein (procedure A)	−59.1	20.2		19.2
In protein (procedure B)	−68.1	11.2	3.2	15.0

^(a)Energy values are reported in kcal/mol. A weak constraint of 0.3 kcal/mol was used to keep the LRA/MC generated water molecules in place. Procedure A corresponds to using standard solvation approach while including water molecules resolved by X-ray, whereas Procedure B corresponds to using our water flooding LRA/MC screening approach. All of these molecular dynamics simulations are performed using the polarizable ENZYMIX force field [36].