Transmission coefficient calculation for proton transfer in triosephosphate isomerase based on the reaction path...

Area of Science:

• Computational Chemistry
• Enzyme Catalysis
• Biophysics

Background:

• Enzymatic reactions are crucial biological processes.
• Understanding enzyme reaction dynamics requires accurate potential energy surfaces.
• Traditional transition state theory may not fully capture enzymatic reaction complexities.

Purpose of the Study:

• To construct and implement a global potential energy surface for enzyme-catalyzed reactions.
• To investigate the dynamical effects on the rate constants of enzymatic proton transfer.
• To assess the influence of protein environment fluctuations on reaction dynamics.

Main Methods:

• Developed a reaction path potential using combined ab initio quantum mechanics and molecular mechanics (QM/MM).
• Constructed a global potential energy surface via interpolation.
• Performed activated molecular dynamics simulations and calculated the transmission coefficient kappa(t) using the reactive flux approach.

Main Results:

• The calculated transmission coefficient kappa(t) was 0.47, indicating significant deviations from transition state theory predictions.
• Protein environment fluctuations had minimal impact on barrier recrossing.
• The transmission coefficient kappa(t) was highly sensitive to fluctuations of atoms in the enzyme's active site.

Conclusions:

• The developed potential energy surface enables accurate simulation of enzyme reaction dynamics.
• Dynamical effects, particularly active site atom fluctuations, are critical for understanding enzymatic reaction rates.
• This study highlights the limitations of transition state theory for complex enzymatic systems.