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Enzymatic Catalytic Reaction Mechanism Calculation


The study of the mechanism of enzymatic catalytic reactions has always been a important subject in chemistry and biology. One of the study of the biggest difficulties and challenges in studying enzymatic reaction mechanism is the multi-scale nature of the enzyme itself. Enzyme folding occurs between microseconds and milliseconds (10-6-10-3 seconds). The movement of structural units such as local α-helix or β-sheets occurs in nanoseconds (10-9 seconds). The movement of residues and the vibration of chemical bonds occur at the level of femtosecond to picosecond (10-15-10-12 seconds). Nowadays, computational simulation based on classical mechanics and quantum theory can greatly compensate for the limitations of experimental methods and provide crucial information such as structure and energy for understanding the mechanism of enzymatic reactions from the atomic level.

Enzymatic Catalytic Reaction Mechanism CalculationFigure 1. A proposed catalytic cycle. (Yates, L. A.; et al. 2015)

Scope of Application

  • Improve the substrate conversion rate.
  • Optimize reaction conditions and improve the efficiency.
  • Design enzyme catalysts with more novel functions.

Our services

Alfa Chemistry has conducted extensive combined quantum/molecular mechanics (QM/MM), dynamic simulation (MD) and density functional theory methods to study various enzyme catalysis processes, and we offer comprehensive investigation of the molecular mechanisms and key residues of the entire enzyme catalysis process. Our fast and high-quality services include the following:

  • QM/MM methods

The QM/MM technology, which is developed based on molecular mechanics and quantum mechanics, has been considered as one of the most reliable computational simulation methods for studying the mechanism of enzyme catalysis. QM/MM simulation can help to provide in-depth understanding of the crucial information such as a series of structure and energy changes involved in the enzymatic catalytic process especially when combined with molecular dynamics simulation. At Alfa Chemistry, our scientists use this technique to study the mechanism of enzyme-catalyzed hydrolysis reaction. We construct various calculation models by designing different protonation states of key residues to obtain the structure and energy information of different reaction pathways, etc. Combined with professional knowledge in computational chemistry, we comprehensively investigate the microscopic mechanism and selectivity of enzyme catalysis.

1. (QM/MM)-based methods in combination with a biased sampling scheme

We simulate chemical reactions occurring inside complex environments and determine the corresponding free energy profile, which provides direct comparison with experimental determined kinetic and equilibrium parameters.

2. Hybrid differential relaxation algorithm

Our teams can obtain more accurate free energy profiles using faster pulling speeds and smaller number of trajectories which can reduce the computational cost.

3. Free energy simulations

We determine the reaction mechanism and our computational analysis can reveal the existence of a transition state, offering new insights on hydrolysis and suggest possible strategies for the creation of therapeutically useful inhibitors.

  • Density functional theory

We use the density functional theory B3LYP method to study the degradation mechanism of hydrolase catalyzed reaction. Our teams establish several active pocket models of different sizes to gain insight into the mechanism of catalytic hydrolysis based on the newly obtained crystal structure. We can also investigate the role of key residues play in the enzymatic catalytic reaction through our accurate calculations using different models. In addition, the hydrolysis mechanism of the glycosidic bond between ribose and ribose obtained can provide a theoretical basis for subsequent mutation experiments and inhibitor design.

Advantages of Our Services

  • We have fully consider each QM region of different sizes to obtain the regulatory effects of key amino acid residues on enzyme reactions in our well-designed QM/MM methods.
  • We can use electronic structure analysis to quantify the relative importance of CHO and OHO non-covalent interactions in imparting reactivity.

Alfa Chemistry provides enzymatic catalytic reaction mechanism calculation services. Our capabilities include QM/MM methods combined with multiple simulations and algorithms. We help to study the reaction results and mechanisms for your innovative scientific research. If you have any questions, please feel free to contact us.


  • Yates, L. A.; et al. Structural plasticity of Cid1 provides a basis for its distributive RNA terminal uridylyl transferase activity. Nucleic Acids Research. 2015, 43(5), 2968-2979.

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