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Why are proteins so important for drug discovery and to tackle disease and find new medicines


nec209

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Well they say by figuring out the exact structure of a protein could sometimes take years and millions of dollars. Why does it take so long to study proteins or the exact structure of a protein?

They also say it takes millions of dollars and very long time and meaning scientists were only able to study a tiny fraction of them. This slowed down research to tackle disease and find new medicines.

Why does it take so long to find the exact structure of a protein?

 

 

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4 hours ago, nec209 said:

Well they say by figuring out the exact structure of a protein could sometimes take years and millions of dollars. Why does it take so long to study proteins or the exact structure of a protein?

They also say it takes millions of dollars and very long time and meaning scientists were only able to study a tiny fraction of them. This slowed down research to tackle disease and find new medicines.

Why does it take so long to find the exact structure of a protein?

 

 

The answer is simple: proteins are complicated. The gold standard is crystallography, which involves purifying proteins and create protein crystals of high quality and to use powerful X-ray lasers to explore their structure. This has many, many challenges, including the fact that many proteins do not like to form ordered crystals (especially membrane proteins). While there are approaches to address it, it remains slow and time consuming. There are hopes that in silico approaches using machine-learning can accelerate the process, and according to some publications, the quality of predictions is getting close to being useful. How well that works with novel structures is in my mind still unclear but might prove itself eventually.

In addition, in many cases having a static structure is not enough. So you want actually see how things bind (once you got the structure you can use models to simulate things, but they might be off, if the binding has unexpected properties), or interact under a given condition (say, within membranes). That increases the complexity even more. 

Forgot to add, the reason why they are important specific for drug development is because they are targets of drugs. If you want to inhibit a certain receptor protein, for example, your drug must be able to bind that receptor under native conditions and thereby block their activity. Without knowing the structure of the receptor you are basically designing blind. With some docking data, you will have a better idea what might theoretically work (whether there are useful in practice is a different matter).

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We could define "living" as the on-going biochemical processes of metabolism (Stop metaboilizng and you're dead.)...Those processses involve enyzymes and their receptors, both are protein in nature...."Disease" is basically some abonormility of that metabolism....

Finding drugs to treat disease has been traditonally acccomplished by making fortuitous observations  of the effects chemicals have (usually from eating plants) on various conditions-- Many indigenous people, for instance observed that nibbling willow bark (contains aspirin) stopped headaches, etc. (You gotta wonder why they were nibbling on willow bark in the first place?)

Those associations are rare and difficult to make....It makes more sense, now that we have the technology, to accurately describe the structure of the enzymes or receptors in the cell and then manufacture chemicals with complementary structures (hand and glove situation) to block the action of the enzyme or receptor...

With technology, we could also find the protein responsible for the disease state, then find the gene responsible for that protein, and then block the specific gene, but that adds a  layer of comlexity and difficulty to the process....They just announced this week that they did it for the first time in regards treating sickel cell anemia, but we already knew the specific gene involved. 

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