Academic Journal
Thermodynamic Activation Parameters for Chemical Reactions in Enzymes and Solution from Computer Simulations at a Single Temperature.
| Title: | Thermodynamic Activation Parameters for Chemical Reactions in Enzymes and Solution from Computer Simulations at a Single Temperature. |
|---|---|
| Authors: | van der Ent F; Department of Cell & Molecular Biology, Uppsala University, Biomedical Center, SE-751 24 Uppsala, Sweden., Demkiv AO; Department of Cell & Molecular Biology, Uppsala University, Biomedical Center, SE-751 24 Uppsala, Sweden., Åqvist J; Department of Cell & Molecular Biology, Uppsala University, Biomedical Center, SE-751 24 Uppsala, Sweden. |
| Source: | Journal of chemical theory and computation [J Chem Theory Comput] 2026 Apr 28; Vol. 22 (8), pp. 4191-4198. Date of Electronic Publication: 2026 Apr 17. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 101232704 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1549-9626 (Electronic) Linking ISSN: 15499618 NLM ISO Abbreviation: J Chem Theory Comput Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Washington, D.C. : American Chemical Society, c2005- |
| MeSH Terms: | Enzymes*/chemistry , Enzymes*/metabolism , Thermodynamics* , Temperature* , Computer Simulation* , Molecular Dynamics Simulation*, Solutions |
| Abstract: | There is considerable interest in being able to address the temperature dependence of enzyme reactions by computer simulations. One reason for this is that enzymes that are adapted to different temperature regimes generally show distinct signatures in terms of their activation enthalpies and entropies, to the extent that it is basically possible to predict whether an enzyme is psychrophilic or mesophilic just by examining these activation parameters. The standard approach to this problem is to calculate reaction free energy profiles at a series of different temperatures. Computational Arrhenius plots can then be constructed from the data, analogous to the experimental procedure. This method has been shown to work well in a number of cases that have examined orthologous pairs of psychrophilic and mesophilic enzymes. The drawback is that the simulations have to be repeated at several temperatures. However, while multitemperature simulations may be computationally demanding they can be informative in revealing deviations from linear Arrhenius behavior. Another issue is that the calculated activation enthalpies obtained in this way cannot be readily decomposed into different energy terms. An alternative approach to the problem would be to just carry out free energy simulations at a single temperature and instead obtain the enthalpy profile by plain averaging of the total energy. The entropy term would then simply be calculated as the difference between free energy and enthalpy. This averaging approach was earlier considered unreliable due to convergence problems for the total energy, even for moderately sized systems. Here, we re-examine the performance of the averaging method for two solution reactions and one enzyme reaction and conclude that it works surprisingly well with sufficient data. This opens up new ways of analyzing nonlinearity of Arrhenius plots in terms of energetics, since the enthalpy is decomposable. |
| References: | Phys Chem Chem Phys. 2006 Dec 14;8(46):5385-95. (PMID: 17119645) Biochemistry. 2008 Sep 23;47(38):10049-57. (PMID: 18759500) Phys Chem Chem Phys. 2015 Jul 14;17(26):16715-8. (PMID: 26073873) Proc Natl Acad Sci U S A. 2016 Jul 12;113(28):7822-7. (PMID: 27354533) Nat Commun. 2015 Jun 01;6:7293. (PMID: 26028237) Proc Natl Acad Sci U S A. 2005 Aug 30;102(35):12395-400. (PMID: 16116099) Sci Adv. 2023 Jun 28;9(26):eadi0963. (PMID: 37379391) Sci Rep. 2015 Oct 26;5:15817. (PMID: 26497916) J Chem Theory Comput. 2022 Oct 11;18(10):6345-6353. (PMID: 36094903) Proc Natl Acad Sci U S A. 1973 Feb;70(2):430-2. (PMID: 4510286) Annu Rev Biochem. 2006;75:403-33. (PMID: 16756497) Nat Commun. 2020 May 26;11(1):2644. (PMID: 32457471) Biochemistry. 2022 May 17;61(10):933-942. (PMID: 35503728) J Chem Theory Comput. 2015 Jul 14;11(7):3499-509. (PMID: 26190950) J Chem Theory Comput. 2025 Feb 11;21(3):1017-1028. (PMID: 39884967) Mol Cell. 2008 Jun 6;30(5):589-98. (PMID: 18538657) Biochemistry. 2000 Aug 15;39(32):9746-53. (PMID: 10933791) Proc Natl Acad Sci U S A. 2016 Mar 1;113(9):2406-11. (PMID: 26755610) J Am Chem Soc. 2003 Aug 27;125(34):10206-12. (PMID: 12926942) Chembiochem. 2006 Jan;7(1):149-57. (PMID: 16342303) PLoS Comput Biol. 2014 Aug 28;10(8):e1003813. (PMID: 25165981) J Chem Theory Comput. 2024 Mar 26;20(6):2582-2591. (PMID: 38452751) J Mol Biol. 1994 Jul 8;240(2):167-76. (PMID: 8028000) J Chem Theory Comput. 2024 Jan 9;20(1):451-458. (PMID: 38112329) J Mol Graph Model. 1998 Aug-Dec;16(4-6):213-25, 261. (PMID: 10522241) |
| Substance Nomenclature: | 0 (Enzymes) 0 (Solutions) |
| Entry Date(s): | Date Created: 20260417 Date Completed: 20260715 Latest Revision: 20260813 |
| Update Code: | 20260813 |
| PubMed Central ID: | PMC13130858 |
| DOI: | 10.1021/acs.jctc.6c00368 |
| PMID: | 41994873 |
| Database: | MEDLINE |
| ISSN: | 1549-9626 |
|---|---|
| DOI: | 10.1021/acs.jctc.6c00368 |