Near attack conformations (NACs) are conformations extending from the ground state (GS) that lie on the transition path of a chemical reaction. Here, we develop a method for computing the thermodynamic contribution to catalysis due to NAC formation in bimolecular reactions, within the limit of a classical molecular dynamics force field. We make use of the Bürgi–Dunitz theory applied to large-scale unbiased all-atom ensemble molecular dynamics simulations. We apply this to HIV-1 protease peptide hydrolysis, known to achieve a rate enhancement of ∼1011 (ΔGcat⧧ ∼ 15 kcal/mol) over the uncatalyzed bimolecular reaction (ΔGnon⧧ ∼ 30 kcal/mol). The ground state consists of a nucleophilic water molecule bound to an octapeptide substrate in the active site. We first observe multiple and reversible binding of a nucleophilic water molecule into the active site giving a free energy of binding of ΔG = −1 kcal/mol to form the GS. The free energy barriers for catalyzed and uncatalyzed NAC formation are both equivalent: ΔGNAC⧧ = 4.6 kcal/mol, constituting ∼30% and ∼15% of the overall barriers, respectively. Therefore, not only does adoption of NACs only account for minor progress along the transition path in both catalyzed and uncatalyzed reactions, but there is no preferential formation of them in the catalyzed reaction. Analysis of the catalytic hydrogen bond network reveals interactions that stabilize the GS; however, subsequent NAC formation does not preferentially favor any of the possible hydrogen bond configurations. This supports the view that the catalytic power of HIV-1 protease is not due to NAC formation.