Disclosed herein are techniques for computationally designing enzymes. These techniques can be used to design variations of naturally occurring enzymes, as well as new enzymes having no natural counterparts. The techniques are based on first identifying functional reactive sites required to promote the desired reaction. Then, hashing algorithms are used to identify potential protein backbone structures (i.e., scaffolds) capable of supporting the required functional sites. These techniques were used to design 32 different protein sequences that exhibited aldol reaction catalytic function, 31 of which are defined in the Sequence Listing. Details of these 31 different synthetic aldolases are provided, including descriptions of how such synthetic aldolases can be differentiated from naturally occurring aldolases.