Atomistic Simulations Decode the Mechanisms of DNA and RNA Processing Enzymes: Function through Motion
1Molecular Modeling and Drug Discovery Lab, Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genoa, Italy.
Accounts of Chemical Research
|July 16, 2026
Summary
Enzymes use precise, coordinated motions for nucleic acid processing, revealing how dynamics define function. Advanced simulations clarify these complex mechanisms, aiding enzyme engineering.
Area of Science:
- Biochemistry and Molecular Biology
- Computational Biology and Biophysics
Background:
- Enzymes like polymerases and nucleases are sophisticated molecular machines essential for life.
- Understanding their catalytic precision requires atomistic insight beyond static structures.
- Static experimental views limit exploration of enzyme conformational space during catalysis.
Purpose of the Study:
- To examine how atomistic multiscale molecular simulations clarify enzymatic mechanisms.
- To highlight the role of dynamics and motion in enzyme function.
- To explore the application of AI-guided enhanced sampling in understanding enzyme catalysis.
Main Methods:
- Atomistic multiscale molecular simulations and free energy calculations.
- AI-guided enhanced sampling methods to overcome simulation limitations.
- Integration of simulation data with structural biology results.
Main Results:
- Dynamics are revealed as a key determinant of enzyme function ('dynamics define function').
- Specific residues in the second coordination shell exhibit coordinated motions crucial for catalysis.
- These motions are finely tuned, small-scale mechanisms, distinct from large allosteric movements.
Conclusions:
- Molecular simulations provide critical insights into the 'move-to-function' mechanisms of enzymes.
- Understanding these precise motions aids in engineering and modulating enzyme activity.
- Findings have implications for nucleic acid chemistry and related scientific activities.
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