观点：应用于酶催化的路径采样方法。
Perspective: Path Sampling Methods Applied to Enzymatic Catalysis.
机构信息
Department of Chemistry and Biochemistry University of Arizona Tucson, Arizona 85721, United States.
出版信息
J Chem Theory Comput. 2022 Nov 8;18(11):6397-6406. doi: 10.1021/acs.jctc.2c00734. Epub 2022 Oct 28.
Abstract
This Perspective reviews the use of Transition Path Sampling methods to study enzymatically catalyzed chemical reactions. First applied by our group to an enzymatic reaction over 15 years ago, the method has uncovered basic principles in enzymatic catalysis such as the protein promoting vibration, and it has also helped harmonize such ideas as electrostatic preorganization with dynamic views of enzyme function. It is now being used to help uncover principles of protein design necessary to artificial enzyme creation.
摘要
本文回顾了过渡态抽样方法在研究酶催化化学反应中的应用。该方法由我们小组于 15 年前首次应用于酶反应，揭示了酶催化中的基本原理，如蛋白质促进振动，还帮助协调了静电预组织与酶功能的动态观点等思想。现在，该方法正被用于帮助揭示人工酶创建所需的蛋白质设计原则。
相似文献
1
Perspective: Path Sampling Methods Applied to Enzymatic Catalysis.
J Chem Theory Comput. 2022 Nov 8;18(11):6397-6406. doi: 10.1021/acs.jctc.2c00734. Epub 2022 Oct 28.
2
Atomistic description of the relationship between protein dynamics and catalysis with transition path sampling.
Methods Enzymol. 2023;685:319-340. doi: 10.1016/bs.mie.2023.03.005. Epub 2023 Apr 19.
3
Changes in protein architecture and subpicosecond protein dynamics impact the reaction catalyzed by lactate dehydrogenase.
J Phys Chem A. 2013 Aug 15;117(32):7107-13. doi: 10.1021/jp400376h. Epub 2013 Mar 12.
4
Advances in optimizing enzyme electrostatic preorganization.
Curr Opin Struct Biol. 2022 Feb;72:1-8. doi: 10.1016/j.sbi.2021.06.006. Epub 2021 Jul 17.
5
Barrier passage and protein dynamics in enzymatically catalyzed reactions.
Eur J Biochem. 2002 Jul;269(13):3103-12. doi: 10.1046/j.1432-1033.2002.03021.x.
6
Atomic detail of chemical transformation at the transition state of an enzymatic reaction.
Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16543-8. doi: 10.1073/pnas.0808413105. Epub 2008 Oct 22.
7
Enzymatic transition states and transition state analog design.
Annu Rev Biochem. 1998;67:693-720. doi: 10.1146/annurev.biochem.67.1.693.
8
Enzymatic transition states and dynamic motion in barrier crossing.
Nat Chem Biol. 2009 Aug;5(8):551-8. doi: 10.1038/nchembio.202.
9
Geometry of Charge Density as a Reporter on the Role of the Protein Scaffold in Enzymatic Catalysis: Electrostatic Preorganization and Beyond.
J Chem Theory Comput. 2023 Feb 14;19(3):694-704. doi: 10.1021/acs.jctc.2c01060. Epub 2022 Dec 23.
10
Protein dynamics and the enzymatic reaction coordinate.
Top Curr Chem. 2013;337:189-208. doi: 10.1007/128_2012_412.
引用本文的文献
1
A Foundational Shift in Models for Enzyme Function.
J Am Chem Soc. 2025 May 7;147(18):14884-14904. doi: 10.1021/jacs.5c02388. Epub 2025 Apr 25.
2
Targeted TPS Shooting Using Computer Vision to Generate Ensemble of Trajectories.
J Chem Theory Comput. 2025 Apr 8;21(7):3353-3359. doi: 10.1021/acs.jctc.4c01725. Epub 2025 Mar 17.
3
Enhanced sampling of protein conformational changes via true reaction coordinates from energy relaxation.
Nat Commun. 2025 Jan 17;16(1):786. doi: 10.1038/s41467-025-55983-y.
4
Substrate Turnover Dynamics Guide Ketol-Acid Reductoisomerase Redesign for Increased Specific Activity.
ACS Catal. 2024 Jun 26;14(14):10491-10509. doi: 10.1021/acscatal.4c01446. eCollection 2024 Jul 19.
5
Myosin-Catalyzed ATP Hydrolysis in the Presence of Disease-Causing Mutations: Mavacamten as a Way to Repair Mechanism.
J Phys Chem B. 2024 May 16;128(19):4716-4727. doi: 10.1021/acs.jpcb.4c01601. Epub 2024 May 6.
本文引用的文献
1
Transition Path Sampling Based Calculations of Free Energies for Enzymatic Reactions: The Case of Human Methionine Adenosyl Transferase and Adenosine Deaminase.
J Phys Chem B. 2022 Jul 28;126(29):5413-5420. doi: 10.1021/acs.jpcb.2c03251. Epub 2022 Jul 13.
2
A two-directional vibrational probe reveals different electric field orientations in solution and an enzyme active site.
Nat Chem. 2022 Aug;14(8):891-897. doi: 10.1038/s41557-022-00937-w. Epub 2022 May 5.
3
Manipulating Reaction Energy Coordinate Landscape of Mechanochemical Diaza-Cope Rearrangement.
Molecules. 2022 Apr 15;27(8):2570. doi: 10.3390/molecules27082570.
4
A Rigorous Method for Identifying a One-Dimensional Reaction Coordinate in Complex Molecules.
J Chem Theory Comput. 2022 May 10;18(5):2836-2844. doi: 10.1021/acs.jctc.2c00132. Epub 2022 Apr 15.
5
Peptide Permeation across a Phosphocholine Membrane: An Atomically Detailed Mechanism Determined through Simulations and Supported by Experimentation.
J Phys Chem B. 2022 Apr 21;126(15):2834-2849. doi: 10.1021/acs.jpcb.1c10966. Epub 2022 Apr 7.
6
A Companion Guide to the String Method with Swarms of Trajectories: Characterization, Performance, and Pitfalls.
J Chem Theory Comput. 2022 Mar 8;18(3):1406-1422. doi: 10.1021/acs.jctc.1c01049. Epub 2022 Feb 9.
7
Peptide Isomerization is Suppressed at the Air-Water Interface.
J Phys Chem Lett. 2022 Jan 20;13(2):574-579. doi: 10.1021/acs.jpclett.1c03837. Epub 2022 Jan 11.
8
Inverse heavy enzyme isotope effects in methylthioadenosine nucleosidases.
Proc Natl Acad Sci U S A. 2021 Oct 5;118(40). doi: 10.1073/pnas.2109118118.
9
String Method with Swarms-of-Trajectories, Mean Drifts, Lag Time, and Committor.
J Phys Chem A. 2021 Sep 2;125(34):7558-7571. doi: 10.1021/acs.jpca.1c04110. Epub 2021 Aug 18.
10
Nudged Elastic Band Method for Molecular Reactions Using Energy-Weighted Springs Combined with Eigenvector Following.
J Chem Theory Comput. 2021 Aug 10;17(8):4929-4945. doi: 10.1021/acs.jctc.1c00462. Epub 2021 Jul 18.
Zotero 插件