Mechanistic rules for de novo design of enzymes
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arXiv
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| Hauptverfasser: | , , |
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| Format: | Preprint |
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2024
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| _version_ | 1866912396385189888 |
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| author | Chatzittofi, Michalis Agudo-Canalejo, Jaime Golestanian, Ramin |
| author_facet | Chatzittofi, Michalis Agudo-Canalejo, Jaime Golestanian, Ramin |
| contents | Enzymes are nano-scale machines that have evolved to drive chemical reactions out of equilibrium in the right place at the right time. Given the complexity and specificity of enzymatic function, bottom-up design of enzymes presents a daunting task that is far more challenging than making passive molecules with specific binding affinities or building nano-scale mechanically active devices. We present a thermodynamically-consistent model for the operation of such a fuelled enzyme, which uses the energy from a favourable reaction to undergo non-equilibrium conformational changes that in turn catalyze a chemical reaction on an attached substrate molecule. We show that enzymatic function can emerge through a bifurcation upon appropriate implementation of momentum conservation on the effective reaction coordinates of the low dimensional description of the enzyme, and thanks to a generically present dissipative coupling. Our results can complement the recently developed strategies for de novo enzyme design based on machine learning approaches. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2408_16639 |
| institution | arXiv |
| publishDate | 2024 |
| record_format | arxiv |
| spellingShingle | Mechanistic rules for de novo design of enzymes Chatzittofi, Michalis Agudo-Canalejo, Jaime Golestanian, Ramin Soft Condensed Matter Statistical Mechanics Biological Physics Chemical Physics Enzymes are nano-scale machines that have evolved to drive chemical reactions out of equilibrium in the right place at the right time. Given the complexity and specificity of enzymatic function, bottom-up design of enzymes presents a daunting task that is far more challenging than making passive molecules with specific binding affinities or building nano-scale mechanically active devices. We present a thermodynamically-consistent model for the operation of such a fuelled enzyme, which uses the energy from a favourable reaction to undergo non-equilibrium conformational changes that in turn catalyze a chemical reaction on an attached substrate molecule. We show that enzymatic function can emerge through a bifurcation upon appropriate implementation of momentum conservation on the effective reaction coordinates of the low dimensional description of the enzyme, and thanks to a generically present dissipative coupling. Our results can complement the recently developed strategies for de novo enzyme design based on machine learning approaches. |
| title | Mechanistic rules for de novo design of enzymes |
| topic | Soft Condensed Matter Statistical Mechanics Biological Physics Chemical Physics |
| url | https://arxiv.org/abs/2408.16639 |