Simulating Chalcogen Bonding Using Molecular Mechanics: A Pseudoatom Approach to Model Ebselen.
The organoselenium compound ebselen has recently been investigated as a treatment for COVID-19, howeverefforts to model ebselen in silico have been hampered by the lack of a efficient and accurate method to assessits binding to biological macromolecules. We present here a Generalized Amber Force Field modification whichincorporates classical parameters for the selenium atom in ebselen, as well as a positively charged pseudoatom tosimulate the sigma?-hole, a quantum mechanical phenomenon that dominates the chemistry of ebselen. Our approachis justified using an energy decomposition analysis of a number DFT optimised structures, which shows that the?sigma-hole interaction is primarily electrostatic in origin. Finally, our model is verified by conducting MD simulationson a number of simple complexes, as well the clinically relevant SOD1, which is known to bind to ebselen..
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Preprint| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
chemRxiv.org - (2021) vom: 18. Nov. Zur Gesamtaufnahme - year:2021 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fellowes, Thomas [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.26434/chemrxiv.12345434 |
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XCH017931797 |
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| 520 | |a The organoselenium compound ebselen has recently been investigated as a treatment for COVID-19, howeverefforts to model ebselen in silico have been hampered by the lack of a efficient and accurate method to assessits binding to biological macromolecules. We present here a Generalized Amber Force Field modification whichincorporates classical parameters for the selenium atom in ebselen, as well as a positively charged pseudoatom tosimulate the sigma?-hole, a quantum mechanical phenomenon that dominates the chemistry of ebselen. Our approachis justified using an energy decomposition analysis of a number DFT optimised structures, which shows that the?sigma-hole interaction is primarily electrostatic in origin. Finally, our model is verified by conducting MD simulationson a number of simple complexes, as well the clinically relevant SOD1, which is known to bind to ebselen. | ||
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