(color online) Residue structures of the three sides around HB1. (a) A-side residue structure of HB1 formed by the sidechains of Lys222, Leu335, and Leu337. Two hydrophobic residues Leu335 and Leu337 form tight hydrophobic binding with the aliphatic stalk of Lys222 sidechain that effectively covers the A side of HB1 and prevents water attack on HB1 from this side. (b) Water attack channel at the B side of HB1. A water attack process is illustrated. (c) A C-side water attack on HB1. The water molecule becomes close to the acceptor oxygen atom of HB1 through forming a water bridge between the backbone oxygens of Glu221 and Glu336.