To further demonstrate the power of CNEO-DFT QM/MM and its potential in biological studies, we next investigated a glutamic acid-glutamate complex (Figure ) in both gas phase and aqueous phase. This complex is a typical lowbarrier hydrogen bond system in which two glutamate anions share a proton, and it is known to play a vital role in some biological systyems. For example, in human transketolase, this complex (between E366' and E160) is believed to participate in a proton wire, which is the structural origin of the enzyme's cooperativity, and in bacteriorhodopsin, a proton pump that uses photon energy to establish transcellular proton gradient, this complex (between E194 and E204) is directly involved in the key pump process by releasing the shared proton to the extracellular environment. Due to the high significance in biological systems, the location of the shared proton in this complex and its real-time dynamics is of particular interest. For human transketolase, high-resolution X-ray crystallography concludes that the proton is almost equally shared by the two carboxylic oxygens of E366' and E160 residues, and the which is much shorter than that of a normal hydrogen bond (2.7~3.1 Å). Note that these high-resolution X-ray crystallography studies can obtain hydrogen positions, which are different from the conventional impression that hydrogen positions cannot be obtained by X-ray crystallography. For bacteriorhodopsin, although the location of the proton is not exactly known, the determined which is even shorter and may imply a more equally shared proton.