Dynamics of an Enzymatic Substitution Reaction in Haloalkane Dehalogenase
Reactive flux molecular dynamics simulations have been carried out using a combined QM/MM potential to study the dynamics of the nucleophilic substitution reaction of dichloroethane by a carboxylate group in haloalkane dehalogenase and in water. We found that protein dynamics accelerates the reactio...
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| Veröffentlicht in: | Journal of the American Chemical Society 2004-02, Vol.126 (5), p.1369-1376 |
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| container_issue | 5 |
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| container_title | Journal of the American Chemical Society |
| container_volume | 126 |
| creator | Nam, Kwangho Prat-Resina, Xavier Garcia-Viloca, Mireia Devi-Kesavan, Lakshmi S Gao, Jiali |
| description | Reactive flux molecular dynamics simulations have been carried out using a combined QM/MM potential to study the dynamics of the nucleophilic substitution reaction of dichloroethane by a carboxylate group in haloalkane dehalogenase and in water. We found that protein dynamics accelerates the reaction rate by a factor of 2 over the uncatalyzed reaction. Compared to the thermodynamic effect in barrier reduction, protein dynamic contribution is relatively small. However, analyses of the friction kernel reveal that the origins of the reaction dynamics in water and in the enzyme are different. In aqueous solution, there is significant electrostatic solvation effect, which is reflected by the slow reorganization relaxation of the solvent. On the other hand, there is no strong electrostatic coupling in the enzyme and the major effect on reaction coordinate motion is intramolecular energy relaxation. |
| doi_str_mv | 10.1021/ja039093l |
| format | Article |
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We found that protein dynamics accelerates the reaction rate by a factor of 2 over the uncatalyzed reaction. Compared to the thermodynamic effect in barrier reduction, protein dynamic contribution is relatively small. However, analyses of the friction kernel reveal that the origins of the reaction dynamics in water and in the enzyme are different. In aqueous solution, there is significant electrostatic solvation effect, which is reflected by the slow reorganization relaxation of the solvent. On the other hand, there is no strong electrostatic coupling in the enzyme and the major effect on reaction coordinate motion is intramolecular energy relaxation.</description><identifier>ISSN: 0002-7863</identifier><identifier>EISSN: 1520-5126</identifier><identifier>DOI: 10.1021/ja039093l</identifier><identifier>PMID: 14759194</identifier><identifier>CODEN: JACSAT</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Biological and medical sciences ; Chemistry ; Computer Simulation ; Exact sciences and technology ; Fourier Analysis ; Fundamental and applied biological sciences. Psychology ; Hydrolases - chemistry ; Hydrolases - metabolism ; Kinetics ; Kinetics and mechanisms ; Mechanisms. Catalysis. Electron transfer. 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Am. Chem. Soc</addtitle><description>Reactive flux molecular dynamics simulations have been carried out using a combined QM/MM potential to study the dynamics of the nucleophilic substitution reaction of dichloroethane by a carboxylate group in haloalkane dehalogenase and in water. We found that protein dynamics accelerates the reaction rate by a factor of 2 over the uncatalyzed reaction. Compared to the thermodynamic effect in barrier reduction, protein dynamic contribution is relatively small. However, analyses of the friction kernel reveal that the origins of the reaction dynamics in water and in the enzyme are different. In aqueous solution, there is significant electrostatic solvation effect, which is reflected by the slow reorganization relaxation of the solvent. On the other hand, there is no strong electrostatic coupling in the enzyme and the major effect on reaction coordinate motion is intramolecular energy relaxation.</description><subject>Biological and medical sciences</subject><subject>Chemistry</subject><subject>Computer Simulation</subject><subject>Exact sciences and technology</subject><subject>Fourier Analysis</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hydrolases - chemistry</subject><subject>Hydrolases - metabolism</subject><subject>Kinetics</subject><subject>Kinetics and mechanisms</subject><subject>Mechanisms. Catalysis. Electron transfer. 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Psychology</topic><topic>Hydrolases - chemistry</topic><topic>Hydrolases - metabolism</topic><topic>Kinetics</topic><topic>Kinetics and mechanisms</topic><topic>Mechanisms. Catalysis. Electron transfer. 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Am. Chem. Soc</addtitle><date>2004-02-11</date><risdate>2004</risdate><volume>126</volume><issue>5</issue><spage>1369</spage><epage>1376</epage><pages>1369-1376</pages><issn>0002-7863</issn><eissn>1520-5126</eissn><coden>JACSAT</coden><abstract>Reactive flux molecular dynamics simulations have been carried out using a combined QM/MM potential to study the dynamics of the nucleophilic substitution reaction of dichloroethane by a carboxylate group in haloalkane dehalogenase and in water. We found that protein dynamics accelerates the reaction rate by a factor of 2 over the uncatalyzed reaction. Compared to the thermodynamic effect in barrier reduction, protein dynamic contribution is relatively small. However, analyses of the friction kernel reveal that the origins of the reaction dynamics in water and in the enzyme are different. In aqueous solution, there is significant electrostatic solvation effect, which is reflected by the slow reorganization relaxation of the solvent. 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| subjects | Biological and medical sciences Chemistry Computer Simulation Exact sciences and technology Fourier Analysis Fundamental and applied biological sciences. Psychology Hydrolases - chemistry Hydrolases - metabolism Kinetics Kinetics and mechanisms Mechanisms. Catalysis. Electron transfer. Models Models, Chemical Molecular biophysics Organic chemistry Physical chemistry in biology Quantum Theory Reactivity and mechanisms Thermodynamics |
| title | Dynamics of an Enzymatic Substitution Reaction in Haloalkane Dehalogenase |
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