All chemists know that the noble gases are chemically inert, except to the most extreme reaction conditions. Paradoxically, several of these gases exhibit a wide range of fascinating biological effects, some of which have been demonstrated in vivo and in the clinic.<br/>Clearly it is impractical to carry out experiments to assess the effect of noble gases on every possible protein target so computational methods have been employed. Given the simplicity of the ligands, and the steady improvement of computational docking algorithms, it is feasible to study a large number of proteins for their likely affinity for the noble gases. The results of simulations will identify which proteins bind the gases most tightly, where the gases bind relative to ligand or cofactor binding sites, thus allowing proteins to be prioritised in terms of potential medical interest.<br/>To this end, we report the results of a comprehensive validation study aiming to identify how accurately computational methods can locate noble gas atoms in proteins in which noble gases were used to solve the phase problem, or were used to probe specific protein channels (e.g. in globins). Using empirical force fields specifically parameterised for noble gas atoms, we show that the experimental binding positions of 399 noble gases can be predicted with accuracies of &gt;95% (within 1A), boding well for the screening of all 60,000 unique proteins for which there are structures in the PDB.

Massive computational docking experiments to identify noble gases target for new ‘atomic drugs’

256th National Meeting (2018)

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