Lucy McGowan
answered on 20 May 2020:
last edited 20 May 2020 7:36 am
Amazing question! Solving the structure of a protein or protein complexes is something that scientists can spend years trying to crack. Knowing this can be really helpful though. If we know the shape of a protein then we can learn more about what the protein does in the body and how it might be related to diseases. We can then use computers to test and predict which compounds and molecules stick to that protein. If they stick, these compounds/molecules could be used as drugs for curing or preventing diseases. This is good if you have a new drug you want to try out – you can screen it against a library of proteins for which the structure is known to see if it sticks. Or, if you have a new protein structure and want to see if any existing drugs stick to it then you can screen the new protein shapes again library of existing drugs to see if they stick. If a compound/molecule sticks to a part of a protein which is important for sending signals or allowing chemical reactions in the body, it can stop the protein from working. This can help to stop a disease in its tracks.
If you know what the protein looks like then you can see the shape of what is known as the ‘active site’ (which is where all the exciting functions of the protein happen) and you can get an insight into how it works (the shape can give you an idea of how the protein works). Often the active site is an excellent target for designing a new medicine to treat the disease caused by the protein going wrong.
Imagine it like a lock and you need to find the right key – if you get a picture of the inside of the lock then you can find keys that will fit. You can then get another picture of the lock with a key that you’ve chosen inside it – then you can see how well it fits. Maybe there’s a bit of the lock that the key doesn’t go into so you might be able to improve the key by changing it so it will go into that empty bit of lock. Or maybe one bit is a bit too close to the lock so if you trim it down it might fit better. Then you can go and find another key that might fit better based upon the structures that you’ve already seen.
This is a good way of going from a medicine that kind of works but maybe has lots of side effects (often caused by the medicine binding to not only the protein you’re looking at but also many others) to making and trying many tiny changes to find something that will bind well to the protein you’re interested in but not to any others and so will have fewer side effects – it’s like the difference between finding a skeleton key that opens many doors and finding a specific key that only opens one door.
Essentially, in biology function (or the way something works) is always related to its shape. I think of proteins just like tools cells use to do their jobs, if their tools break then they can’t do their job properly and that results in a disease, or in the case of a bacteria or virus we want to stop their tools working so they can’t infect us or make us ill.
Just like the tools in your house, if I described something as “having a metal part, a handle, it has to move to work and you can use it to put up shelves” what would you picture? some people would think of a hammer, others a screwdriver, some people would think of an electric drill – maybe there’s even other tools that fit that description I haven’t thought of! Hopefully you’ll agree with me that hammers and screwdrivers have very different shapes, and that relates to how they work. Hammers have a flat edge that hits a nail and works by swinging through the air, whereas screw drivers have a cross shape that fits into the head of a screw and work by twisting around. Proteins in the body are just the same! One will have a different shaped active site (where it does it’s job) compared to another based on what its job is or how it does that job.
Now say you wanted to stop all screwdrivers from working, but leave all hammers alone, what kind of thing would you invent? Screws and nails are too similar looking to focus on them, but you could make something that would fit on the end of a screwdriver and stop it from being able to fit into a screw head, but that thing would never be able to fit onto a hammer and stop it from working. Again, it’s just the same for proteins, design a medicine that fits perfectly into one and it (usually) doesn’t affect any other protein functions.
Comments
Alex commented on :
Hi! this is the area I research!!
Essentially, in biology function (or the way something works) is always related to its shape. I think of proteins just like tools cells use to do their jobs, if their tools break then they can’t do their job properly and that results in a disease, or in the case of a bacteria or virus we want to stop their tools working so they can’t infect us or make us ill.
Just like the tools in your house, if I described something as “having a metal part, a handle, it has to move to work and you can use it to put up shelves” what would you picture? some people would think of a hammer, others a screwdriver, some people would think of an electric drill – maybe there’s even other tools that fit that description I haven’t thought of! Hopefully you’ll agree with me that hammers and screwdrivers have very different shapes, and that relates to how they work. Hammers have a flat edge that hits a nail and works by swinging through the air, whereas screw drivers have a cross shape that fits into the head of a screw and work by twisting around. Proteins in the body are just the same! One will have a different shaped active site (where it does it’s job) compared to another based on what its job is or how it does that job.
Now say you wanted to stop all screwdrivers from working, but leave all hammers alone, what kind of thing would you invent? Screws and nails are too similar looking to focus on them, but you could make something that would fit on the end of a screwdriver and stop it from being able to fit into a screw head, but that thing would never be able to fit onto a hammer and stop it from working. Again, it’s just the same for proteins, design a medicine that fits perfectly into one and it (usually) doesn’t affect any other protein functions.
I wrote a blog piece about how this kind of research is being used to target proteins from covid-19 if you want to give it a read! https://pintofscience.co.uk/blog/the-improtance-of-proteins-in-covid-19/
anon-254948 commented on :
Thank you!! I’ll be sure to have a look.
anon-254948 commented on :
Wow thank you so much for all your replies! I understand it a lot better now.