Exploration of biochemical reactivity with a QM/MM growing string method

Area of Science:

• Computational Chemistry
• Biophysical Chemistry

Background:

• Quantum mechanics/molecular mechanics (QM/MM) is crucial for studying complex chemical reactions.
• Generating accurate reaction pathways in QM/MM can be challenging and require significant user input.
• Existing methods like adiabatic mapping may produce discontinuous energy profiles, necessitating remapping.

Purpose of the Study:

• To implement the single-ended growing string method within a QM/MM framework.
• To automate and improve the quality of QM/MM reaction pathway generation.
• To provide a more robust alternative to adiabatic mapping for complex systems.

Main Methods:

• Implementation of the single-ended growing string method using a hybrid internal/Cartesian coordinate scheme.
• Integration into the in-house QM/MM package, QoMMMa.
• Validation using the Claisen rearrangement catalyzed by chorismate mutase.

Main Results:

• Successful implementation of the growing string method in QM/MM.
• Accurate prediction of the transition state and barrier height for the model reaction.
• Over 88% of generated pathways were of production quality.
• Fewer discontinuities in pathways compared to adiabatic mapping.

Conclusions:

• The QM/MM growing string method is effective for generating high-quality reaction pathways.
• This method reduces user input and the need for remapping compared to adiabatic mapping.
• It represents a significant advancement for computational studies of enzyme-catalyzed reactions.