10 years ago I worked with a few coworkers on a protein search algorithm through the PDB (finding structure motifs with flexible and more stable components). It was a multi-month effort and our tool eventually vanished into the failed venture backed bio company. This type of problem is trivial compared to energy minimization (simulated structure) efforts.
Mapping problems to an interface where thousands or millions of humans and computers can tackle them generates a sense of awe each time I read about it.