Modeling of transition state by molecular dynamic method often requires modification of the force field parameters to describe energy profile accurately. In this work, we avoided the modification by modeling a series of mutants at binding-related site. In predicting the catalytic efficiency (k_cat/K_m) of the mutants of mandelate racemase (MR), the prediction performance of three energy subsets was investigated. It was indicated that the interaction-energy subset exhibited better prediction performance than whole-system subset and binding-site subset in both quantity and trend. When prediction error (PE) criterion was equal to 5%, 10 out of 12 samples were predicted correctly within interaction-energy subset, which demonstrated a great application potential of this method in prediction of enzyme catalytic efficiency and enzyme rational design.

Key words: Molecular dynamic; Mandelate racemase; Catalytic efficiency; Free energy; Rational design.