Congrats! Cryo-EM is the tool that basically gave birth to integrative structural biology. Our understanding of how viruses attach to healthy cells, or how blastocysts differentiate into stem cells is all contingent upon our ability to observe these processes in vivo. And as we push ever further down into the atomic scale, using better electron detectors and more intelligent Bayesian estimations, many hidden mysteries of cell functioning will soon be revealed.
For example, seeing the structure and attack vector of the Plasmodium falciparum parasite that causes severe malaria has led to the design for an inhibitor.
The cryo-EM structure of the Plasmodium falciparum 20S proteasome and its use in the fight against malaria.
What are some good introductory texts/resources to read to get up to your level of understanding in these topics? Is this a biochem, virology, molecular bio area of study?
As a former chemistry student from way back, this is awesome stuff that was science-fiction back then. Imaging chemical reactions in mid-flight is one of those things people have always wanted.
The computational problem for solving Cryo-EM structures is an interesting one. The current state-of-the-art approach is essentially an EM algorithm for classifying and estimating the orientations of the images, but it utilises a fairly brute-force approach (and thus quite computationally expensive). There is probably a lot of room here for further improvements, such as better or faster approximations, or using different statistical/machine learning approaches, as well as incorporating more chemical/structural knowledge into the process.
A bit off topic. Say, 5-10 years ago I read about someone winning a nobel prize for something he did regarding blood. When he was asked in the interview how he came about the discovery, he replied having imagined himself as that particular "compound" traveling through the blood stream while on Acid. Later on I tried searching for that to see who it was but couldn't find it. Now I wonder if it's true.
This is not prediction, it's structure determination. Though there is a lot of computation
and modelling involved, it's much more like X-ray crystallography and NMR than ab initio structure prediction. It's based on actual, measured data, not on computation alone.
It is very impressive that they managed to get the resolution of the method into a range comparable to the other conventional methods.
For example, seeing the structure and attack vector of the Plasmodium falciparum parasite that causes severe malaria has led to the design for an inhibitor.
The cryo-EM structure of the Plasmodium falciparum 20S proteasome and its use in the fight against malaria.
https://www.ncbi.nlm.nih.gov/pubmed/27286897
Hexahydroquinolines are antimalarial candidates with potent blood-stage and transmission-blocking activity
https://www.nature.com/articles/s41564-017-0007-4