We present a method to rapidly identify hydrogen-mediated interactions in proteins (e.g., hydrogen bonds, hydrogen bonds, water-mediated hydrogen bonds, salt bridges, and aromatic π-hydrogen interactions) through heavy atom geometry alone, that is, without needing to explicitly determine hydrogen atom positions using either experimental or theoretical methods. By including specific real (or virtual) partner atoms as defined by the atom type of both the donor and acceptor heavy atoms, a set of unique angles can be rapidly calculated. By comparing the distance between the donor and the acceptor and these unique angles to the statistical preferences observed in the Protein Data Bank (PDB), we were able to identify a set of conserved geometries (15 for donor atoms and 7 for acceptor atoms) for hydrogen-mediated interactions in proteins. This set of identified interactions includes every polar atom type present in the Protein Data Bank except OE1 (glutamate/glutamine sidechain) and a clear geometric preference for the methionine sulfur atom (SD) to act as a hydrogen bond acceptor. This method could be readily applied to protein design efforts.

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