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

2020-05-22T04:47:18Z (GMT) 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.