Impact of enzyme motion on activity

Area of Science:

• Biochemistry
• Computational Chemistry
• Molecular Biophysics

Background:

• Enzyme motion is increasingly recognized as crucial for enzymatic activity.
• Existing models often overlook the interplay between different types of enzyme motion.

Purpose of the Study:

• To investigate the relationship between enzyme motion and enzymatic activity.
• To develop a theoretical framework that incorporates quantum effects and distinguishes motion types.

Main Methods:

• A hybrid theoretical approach combining electronic and nuclear quantum effects.
• Distinguishing between promoting motions (affecting activation energy) and dynamical motions (affecting barrier recrossing).
• Applying the method to hydride transfer in liver alcohol dehydrogenase and dihydrofolate reductase.

Main Results:

• Identified and characterized key enzyme motions involved in hydride transfer reactions.
• Demonstrated that enzyme motion influences both activation free energy and barrier recrossing.
• Proposed a network of coupled promoting motions governing enzymatic reactions.

Conclusions:

• Enzyme motion is a critical determinant of enzymatic reaction rates and mechanisms.
• The developed hybrid theoretical approach provides insights into enzyme dynamics.
• Findings have significant implications for rational protein engineering and drug design strategies.