Simulations of Proton Transfer and Hydride Transfer Reactions in Proteins

Abstract

Simulations of proton transfer and hydride transfer reactions by the Empirical Valence Bond method are described. The use of this method in examination of Linear Free Energy Relationships (LFER) and in obtaining quantum mechanical rate constants is illustrated. It is pointed out that LFERs are probably valid even in enzymatic reactions since computer simulations indicate that the electrostatic response of protein active sites can be described by the linear response approximation. The validity of LFERs in proteins should provide a powerful tool in protein design, although it is important to realize that such relationships are much more valid for transitions between different resonance structures than for transitions between reactants and product states.