To mimic the real biological environment, we should ideally embed the two amino acids in relatively rigid protein backbones. However, for this proof-ofconcept study, we simplified the problem by applying distance constraints to two pairs of carbon atoms according to the experimental X-ray structure of human transketolase. Specifically, the distance between the two α-carbons is constrained to 7.84 Å and the distance between the two carboxylic carbons is constrained to 9.01 Å. (Figure ) These constraints serve a role similar to the protein backbones, which preserve the intercarboxylic hydrogen bond and prevent strong conformational changes that would be unnatural in a protein environment.