Towards accurate ab inito QM/MM calculations of free-energy profiles of enzymatic reactions

The evaluation of ab inito QM/MM free-energy surfaces and activation free energies of reactions in enzymes and in solutions is carried out by using the empirical valence bond (EVB) method as a reference potential and then using linear response approximation (LRA). This new method evaluates the free energy associated with both the substrate and the solvent and helps in obtaining a free-energy barrier that reflects the solute entropy properly.