Automated Path Searching Reveals the Mechanism of Hydrolysis Enhancement by T4 Lysozyme Mutants
Abstract
:1. Introduction
2. Methods
2.1. Initial Structures and Transition Paths for Three Variants of T4L
2.2. Path Optimization by TAPS
2.2.1. Flowchart of TAPS Optimization
2.2.2. Path Optimization Convergence Check
- (a)
- (b)
- the visualization of the optimization process via the projection of all paths on a low-dimensional space generated by multidimensional scaling (MDS) [66] (more details are provided in the Supplementary Materials and Ref. [34]).
2.3. Free-Energy Calculation
3. Results
3.1. The Main Activation Mechanism for the Three T4L Variants
3.2. Enhancing the Hydrolysis of T4L through Three Substitutions
3.3. Transition Mechanism of T4L
3.3.1. Step One: F114 Flipping
3.3.2. Step Two: α0/α1 Rearrangement
3.3.3. Step Three: Final Refinement
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Xi, K.; Zhu, L. Automated Path Searching Reveals the Mechanism of Hydrolysis Enhancement by T4 Lysozyme Mutants. Int. J. Mol. Sci. 2022, 23, 14628. https://doi.org/10.3390/ijms232314628
Xi K, Zhu L. Automated Path Searching Reveals the Mechanism of Hydrolysis Enhancement by T4 Lysozyme Mutants. International Journal of Molecular Sciences. 2022; 23(23):14628. https://doi.org/10.3390/ijms232314628
Chicago/Turabian StyleXi, Kun, and Lizhe Zhu. 2022. "Automated Path Searching Reveals the Mechanism of Hydrolysis Enhancement by T4 Lysozyme Mutants" International Journal of Molecular Sciences 23, no. 23: 14628. https://doi.org/10.3390/ijms232314628