QUASI: A general purpose implementation of the QM/MM approach and its application to problems in catalysis

Sherwood, Paul; Vries, Alex H. de; Guest, Martyn F.; Schreckenbach, Georg; Catlow, C. Richard A.; French, Samuel A.; Sokol, Alexey A.; Bromley, Stefan T.; Thiel, Walter; Turner, Alexander; Billeter, Salomon R.; Terstegen, Frank; Thiel, Stephan; Kendrick, John; Rogers, Stephen C.; Casci, John L.; Watson, M.; King, Frank D.; Karlsen, Elly J.; Sjøvoll, Merethe; Fahmi, Adil; Schäfer, Ansgar; Lennartz, Christian

doi:10.1016/s0166-1280(03)00285-9

Cited by 950 publications

(981 citation statements)

References 93 publications

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“…Chemshell version 3.7 57,58 was used for all QM/MM calculations. Scripts in Python and Tcl to convert the GROMACS MM model format to Chemshell format were written (available as supporting information).…”

Section: Model Preparation and Solvationmentioning

confidence: 99%

QM/MM Study of the Nitrogenase MoFe Protein Resting State: Broken-Symmetry States, Protonation States, and QM Region Convergence in the FeMoco Active Site

2017

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Nitrogenase is one of the most fascinating enzymes in nature, being responsible for all biological nitrogen reduction. Despite decades of research it is among the enzymes in bioinorganic chemistry whose mechanism is the most poorly understood. The MoFe protein of nitrogenase contains an iron-molybdenum-sulfur cluster, FeMoco, where N 2 reduction takes place. The resting state of FeMoco has been characterized by crystallography, multiple spectroscopic techniques and theory (broken-symmetry density functional theory) and all heavy atoms are now characterized. The cofactor charge, however, has been controversial, the electronic structure has proved enigmatic and little is known about the mechanism. While many computational studies have been performed on FeMoco, few have taken the protein environment properly into account. In this study, we put forward QM/MM models of the MoFe protein from Azotobacter vinelandii, centered on FeMoco. By a detailed analysis of the FeMoco geometry and comparing to the atomic resolution crystal structure we conclude that only the [MoFe 7 S 9 C] 1-charge is a possible resting state charge. Further we find that, of the 3 lowest energy broken-symmetry solutions of FeMoco the BS7-235 spin isomer (where 235 refers to Fe atoms that are "spin-down") is the only one that can be reconciled with experiment. This is revealed by a comparison of the metal-metal distances in the experimental crystal structure, a rare case of spin-coupling phenomena being visible through the molecular structure. This could be interpreted as the enzyme deliberately stabilizing a specific electronic state of the cofactor, possibly for tuning specific reactivity on specific metal atoms. Finally, we show that the alkoxide group on the Mo-bound homocitrate must be protonated under resting state conditions; the presence of which has implications regarding the nature of FeMoco redox states as well as for potential substrate reduction mechanisms.3

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Section: Model Preparation and Solvationmentioning

confidence: 99%

QM/MM Study of the Nitrogenase MoFe Protein Resting State: Broken-Symmetry States, Protonation States, and QM Region Convergence in the FeMoco Active Site

2017

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“…This confirms previous claims on the stabilizing role of ribose aliphatic hydrogens as "non-canonical" hydrogen bond donors in modified oligonucleotides. 32,33 Impact of the C2'O2' Torsion on the Global RNA Structure. We performed MD simulations of a variety of standard RNA motives (see Supplementary Methods 2) to see whether the most accurate RNA forcefield is able to capture the  distribution found in database analysis and QM/MM calculations.…”

Section: ~12 Kcal/mol (mentioning

confidence: 99%

Small Details Matter: The 2′-Hydroxyl as a Conformational Switch in RNA

et al. 2016

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While DNA is mostly a primary carrier of genetic information and displays a regular duplex structure, RNA can form very complicated and conserved 3D structures displaying a large variety of functions, such as being an intermediary carrier of the genetic information, translating such information into the protein machinery of the cell, or even acting as a chemical catalyst. At the base of such functional diversity is the subtle balance between different backbone, nucleobase, and ribose conformations, finely regulated by the combination of hydrogen bonds and stacking interactions. Although an apparently simple chemical modification, the presence of the 2'OH in RNA has a profound effect in the ribonucleotide conformational balance, adding an extra layer of complexity to the interactions network in RNA. In the present work, we have combined database analysis with extensive molecular dynamics, quantum mechanics, and hybrid QM/MM simulations to provide direct evidence on the dramatic impact of the 2'OH conformation on sugar puckering. Calculations provide evidence that proteins can modulate the 2'OH conformation to drive sugar repuckering, leading then to the formation of bioactive conformations. In summary, the 2'OH group seems to be a primary molecular switch contributing to specific protein-RNA recognition.

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“…[1][2][3] The division of a large system into a quantum mechanical ͑QM͒ and a molecular mechanical ͑MM͒ region ͑QM/MM͒ allows the reactive center to be studied with a high-level theory, while the effects of the environment ͑structural and electrostatic͒ are calculated at the computationally less-demanding MM level. QM/MM was first developed in the 1970s, 4 and numerous variations of the method have been devised since ͑see Ref.…”

Section: Introductionmentioning

confidence: 99%

Hydrogenation of CO on a silica surface: An embedded cluster approach

Goumans

Catlow

Brown

2008

The Journal of Chemical Physics

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Hydrogenation of CO on a silica surface: an embedded cluster approach Article (Published Version) http://sro.sussex.ac.uk Copyright and reuse:Sussex Research Online is a digital repository of the research output of the University.Copyright and all moral rights to the version of the paper presented here belong to the individual author(s) and/or other copyright owners. To the extent reasonable and practicable, the material made available in SRO has been checked for eligibility before being made available.Copies of full text items generally can be reproduced, displayed or performed and given to third parties in any format or medium for personal research or study, educational, or not-for-profit purposes without prior permission or charge, provided that the authors, title and full bibliographic details are credited, a hyperlink and/or URL is given for the original metadata page and the content is not changed in any way. The sequential addition of H atoms to CO adsorbed on a siliceous edingtonite surface is studied with an embedded cluster approach, using density functional theory for the quantum mechanical ͑QM͒ cluster and a molecular force field for the molecular mechanical ͑MM͒ cluster. With this setup, calculated QM/MM adsorption energies are in agreement with previous calculations employing periodic boundary conditions. The catalytic effect of the siliceous edingtonite ͑100͒ surface on CO hydrogenation is assessed because of its relevance to astrochemistry. While adsorption of CO on a silanol group on the hydroxylated surface did not reduce the activation energy for the reaction with a H atom, a negatively charged defect on the surface is found to reduce the gas phase barriers for the hydrogenation of both CO and H 2 C v O. The embedded cluster approach is shown to be a useful and flexible tool for studying reactions on ͑semi-͒ionic surfaces and specific defects thereon. The methodology presented here could easily be applied to study reactions on silica surfaces that are of relevance to other scientific areas, such as biotoxicity of silica dust and geochemistry.

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QUASI: A general purpose implementation of the QM/MM approach and its application to problems in catalysis

Cited by 950 publications

References 93 publications

QM/MM Study of the Nitrogenase MoFe Protein Resting State: Broken-Symmetry States, Protonation States, and QM Region Convergence in the FeMoco Active Site

QM/MM Study of the Nitrogenase MoFe Protein Resting State: Broken-Symmetry States, Protonation States, and QM Region Convergence in the FeMoco Active Site

Small Details Matter: The 2′-Hydroxyl as a Conformational Switch in RNA

Hydrogenation of CO on a silica surface: An embedded cluster approach

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