Shape complementarity, binding-site dynamics, and transition state stabilization: A theoretical study of Diels-Alder catalysis by antibody 1E9

Antibody 1E9 is a protein catalyst for the Diels-Alder reaction between tet rachlorothiophene dioxide and N-ethylmaleimide. Quantum mechanical calculat ions have been employed to study the 1E9-catalyzed Diels-Alder reaction in the gas phase. The transition states and intermediates were all determined at the B3LYP/6-31G*//HF/6-31G* level. The cycloaddition step is predicted t o be rate-determining, and the endo reaction pathway is strongly favored. B inding of the reactants and the transistion states to antibody 1E9 was inve stigated by docking and molecular dynamics simulations. The linear interact ion energy (LIE) method was adopted to estimate the free energy barrier of the 1E9-catalyzed Diels-Alder reaction. The catalytic efficiency of antibod y 1E9 is achieved by enthalpic stabilization of the transition state, near- perfect shap