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

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Computational Methods for Macromolecules: Challenges and Applications

Part of the book series: Lecture Notes in Computational Science and Engineering ((LNCSE,volume 24))

Abstract

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.

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Author notes

  1. Yingkai Zhang

    Present address: Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, CA, 92093-0365, USA

  2. Haiyan Liu

    Present address: School of Life Science, University of Science and Technology of China, Hefei, Anhui, 230026, China

Authors and Affiliations

  1. Department of Chemistry, Duke University, Durham, North Carolina, 27708, USA

    Yingkai Zhang, Haiyan Liu & Weitao Yang

Authors
  1. Yingkai Zhang
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  2. Haiyan Liu
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  3. Weitao Yang
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Editors and Affiliations

  1. Department of Chemistry, Courant Institute of Mathematical Sciences, New York University, 251 Mercer Street, New York, NY, 10012, USA

    Tamar Schlick  & Hin Hark Gan  & 

  2. Howard Hughes Medical Institute, 251 Mercer Street, New York, NY, 10012, USA

    Tamar Schlick  & Hin Hark Gan  & 

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© 2002 Springer-Verlag Berlin Heidelberg

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Zhang, Y., Liu, H., Yang, W. (2002). Ab Initio QM/MM and Free Energy Calculations of Enzyme Reactions. In: Schlick, T., Gan, H.H. (eds) Computational Methods for Macromolecules: Challenges and Applications. Lecture Notes in Computational Science and Engineering, vol 24. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-56080-4_14

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  • DOI: https://doi.org/10.1007/978-3-642-56080-4_14

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-43756-7

  • Online ISBN: 978-3-642-56080-4

  • eBook Packages: Springer Book Archive

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