Why We Like Proteins?
More than 95% of known drug targets are proteins, involved in roughly 93% of drug-target interactions.
But, traditional methods of determining protein structures like the examples given below are extremely expensive and time consuming.
![](https://static.wixstatic.com/media/c837a6_a56caf65f5424508937c5d7a4ced1619~mv2.jpg/v1/fill/w_391,h_220,al_c,q_80,usm_0.66_1.00_0.01,enc_auto/c837a6_a56caf65f5424508937c5d7a4ced1619~mv2.jpg)
Single Crystal X ray Diffraction
Approximately
130,000 protein structures determined thus far
Limitations​
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Not all proteins can be crystallised; crystallisation is a major bottleneck.
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Determining protein structure needs around 100 mg of pure protein and a year of work by a small team.
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Lab work is time-consuming.
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A protein crystal can yield multiple states of a protein.
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Researchers often rely on Argonne National Lab for the Advanced Photon Source.
Limitations​
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$5M initial capital and $500,000 annual operating costs may be required.
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Structure determination of biological macromolecules is limited to large complexes or low-resolution models.
![](https://static.wixstatic.com/media/c837a6_e166632dd5264456b9b5beba3bd949dd~mv2.jpg/v1/fill/w_391,h_220,al_c,q_80,usm_0.66_1.00_0.01,enc_auto/c837a6_e166632dd5264456b9b5beba3bd949dd~mv2.jpg)
Cryo Electron Microscopy
Approximately 8000 protein structures determined thus far
![](https://static.wixstatic.com/media/c837a6_a56caf65f5424508937c5d7a4ced1619~mv2.jpg/v1/fill/w_391,h_220,al_c,q_80,usm_0.66_1.00_0.01,enc_auto/c837a6_a56caf65f5424508937c5d7a4ced1619~mv2.jpg)
'Nuclear Magnetic Resonance'
Approximately'
14,00 protein structures determined thus far
Limitations​
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It is an expensive technique because the protein has to be enriched with radionuclides by feeding 15-N labeled Ammonium Chloride and 13-C labeled Glucose to bacteria.
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Variable labeling efficiency.
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Complex NMR spectra for high-molecular-weight biomolecules are challenging to interpret.