Ab Initio QM/MM and Free Energy Calculations of Enzyme Reactions

  • Yingkai Zhang
  • Haiyan Liu
  • Weitao Yang
Part of the Lecture Notes in Computational Science and Engineering book series (LNCSE, volume 24)


A recently developed computational approach to studying enzyme reactions is reviewed. This approach consists of three major components: a pseudobond ab initio QM/MM method which provides a consistent and well-defined potential energy surface, an efficient iterative optimization procedure which determines the reaction paths with a realistic enzyme environment, and the free energy calculations which take account of the fluctuation of enzyme system. The review describes the applications of this QM/MM free energy approach to simulate reactions in two enzymes: enolase and triosephosphate isomerase (TIM). The calculations on enolase provide the insight on how the structure of the enolase active site organized to catalyze two different reaction to achieve overall catalytic efficiency. The study of TIM indicated a dual pathway mechanism and a low-barrier hydrogen bond (LBHB) formed in the enediol intermediate. The LBHB is found to be very short with a distance of 2.46 Angstrom between two oxygen donor atoms, but its strength is only about 3–4 kcal/mol stronger than the normal hydrogen bond and even less than the ionic asymmetric hydrogen bond. That is much less than the value of 10–20 kcal/mol in the LBHB hypothesis.


Reaction Path Free Energy Calculation Triosephosphate Isomerase Minimum Energy Path Free Energy Profile 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2002

Authors and Affiliations

  • Yingkai Zhang
    • 1
  • Haiyan Liu
    • 1
  • Weitao Yang
    • 1
  1. 1.Department of ChemistryDuke UniversityDurhamUSA

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