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Hierarchy of Biological Complexity Macromolecular machines Protein and nucleic acid structure Sequences. " It is very easy to answer many of these fundamental biological questions; you just look at the thing!... Make the microscope one hundred times more
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Hierarchy of Biological Complexity Macromolecular machines Protein and nucleic acid structure Sequences
"It is very easy to answer many of these fundamental biological questions; you just look at the thing!... Make the microscope one hundred times more powerful, and many problems of biology would be made very much easier. I exaggerate, of course, but the biologists would surely be very thankful to you — and they would prefer that to the criticism that they should use more mathematics.“ Richard P. Feynman. From There's Plenty of Room at the Bottom, a lecture given to the American Physical Society in 1959.
Structure: what does it look like? Low resolution data on entire complex (EM) + High resolution data on individual components (x-ray / NMR) High resolution model of complex Verification of model by difference mapping / labeling
Mt-K.ADP Mt-K.ADP.Pi Mt-K.ATP Mt-K Mt-K.ADP Pi Mt K.ADP ATP ADP
Mechanism: how does it work? Hypothesis driven Attachment of reporters to visualize conformational changes Trapping in defined parts of its cycle
Raft 7.6 A 88,000x 100000x 11.5 A
Leginon I setup for TMV data acquisition 550x 1700x 100000x 7-15 e/A2 0.002 e/A2 0.05 e/A2 Typical doses accumulated during automated acquisition