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Simulating Chalcogen Bonding Using Molecular Mechanics: A Pseudoatom Approach to Model Ebselen.

submitted on 21.05.2020 and posted on 22.05.2020 by Thomas Fellowes, JONATHAN WHITE
The organoselenium compound ebselen has recently been investigated as a treatment for COVID-19, however
efforts to model ebselen in silico have been hampered by the lack of a efficient and accurate method to assess
its binding to biological macromolecules. We present here a Generalized Amber Force Field modification which
incorporates classical parameters for the selenium atom in ebselen, as well as a positively charged pseudoatom to
simulate the sigma?-hole, a quantum mechanical phenomenon that dominates the chemistry of ebselen. Our approach
is 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 simulations
on a number of simple complexes, as well the clinically relevant SOD1, which is known to bind to ebselen.


Email Address of Submitting Author


University of Melbourne



ORCID For Submitting Author


Declaration of Conflict of Interest

There are no conflicts of interest to declare