Minimum energy path methods and reactivity for enzyme reaction mechanisms: a perspective
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Neil R. McFarlane
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Jeremy N. Harvey
Abstract
In this perspective article, we discuss the link between minimum energy paths and activation parameters for reactions on complex potential energy surfaces involving many possible local minima, as are typically found for enzyme-substrate complexes. Such systems are frequently tackled with hybrid QM/MM methods in order to characterize reactivity. The link between local energy barriers along a minimum energy path, the so-called exponential average of such local energy barriers, and multiconformational transition state theory is discussed. Also, it is shown that in case of positive skewness of the distribution of barrier heights across sets of minimum energy paths, exponential averaging converges relatively quickly with the number of paths used.
Funding source: KU Leuven
Award Identifier / Grant number: C14/22/087
Acknowledgments
The authors thank Profs. Julianna Olah and Ulf Ryde for helpful discussions. They also acknowledge funding from KU Leuven research through grant C14/22/087.
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Research ethics: Not applicable.
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Informed consent: Not applicable.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission. The text was written by both authors. The Monte Carlo analysis was performed by N.M.
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Use of Large Language Models, AI and Machine Learning Tools: Non declared.
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Conflict of interest: The authors state no conflict of interest.
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Research funding: Yes, from KULeuven research funding, grant ref. C14/22/087.
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Data availability: Not applicable.
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