Computer Simulation of Enzymatic Reactions

Our strategy in modeling ezymatic reactions is demonstrated by considering two complimentary approaches, which are based on the powerful EVB method. The first approach uses the X-ray coordinates at their face value and estimates the reaction potential surface by using a simplified and efficient microscopic dipolar model for the solvent. The second approach (which became practical only upon the emergence of supercomputers) uses a surface constrained all atom solvent model, molecular dynamics (MD) and the umbrella sampling method to evaluate the actual free energy barrier. Both approaches indicate that the correct evaluation of the “solvation energy” of the ionic resonance structures is the key for understanding enzyme catalysis. The MD version of the EVB method is used in a preliminary study of the validity of linear free-energy relationships in enzymatic reactions. This study supports the ad hoc assumptions introduced in the simplified method.