Since you want to think big, I would suggest as a challenge to solve
the 3-D atomic structure of a human chromosome. Not the proteins
encoded by the DNA, but the 3-D structure of an entire chromosome.
Only about 1 percent of DNA codes for proteins. To understand gene
regulation and what makes a human different from a mouse, understanding
the 3-D organization of an entire chromosome will be necessary.

The first protein structure in 1958 (myoglobin) had about 1200 atoms.
Now, about 60 years later we have the structure of the 70S ribosome (6ND5)
with about 300000 atoms - about 250 times larger than myoglobin.
Chromosomes are quite a bit larger, with about 8 billion atoms
each - over 26000 times larger than the 70S ribosome. This won't be
solved with X-ray crystallography, but perhaps with a trillion dollar
cryo-em microscope / detector combined with other technologies it
might.

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