Protein Structures and Structural Proteomics

[donkey]

Hey, please excuse any naivety that follows. I was wondering if anyone here had much familiarity with protein structure determination or anything else relating to protein structure and function.

 

I'm really interested in the 3D structures of proteins and would be interested in possibly persuing this as a PhD but I'm not sure which areas of research there really are available. I'm most interested in things like structure based drug design (among other related things such as understanding enzyme mechanisms by investigating their 3D structure) and generally using knowledge of protein structures to understand how things work. I am bit worried that to do this I would have to be the one spending a long time producing these structures - although this could be really exciting I'm quite worried that it'll be time consuming and complicated. This could get dangerously like physics. I'm not great at maths and am a bit daunted by having to master x-ray crystalography or NMR. How hard is it?

 

I've not decided i don't want to determine structures I just wondered if there were a lot of people doing related stuff but not actually determining their own structures.

 

I'm interested in how proteins fold and would be really interested in making a synthetic protein/enzyme. I know this is perhaps a pipe dream and it may be a long time before the most basic proteins are designed but I would be interested to know what you would call this type of science? Does anyone know where it would be done outside of industry... if anywhere?

[Yggdrasil]

I work in a lab at the University of California, Los Angeles Molecular Biology Institute as an undergrad doing research in the field of structural biology. If you're interested in doing research in that field, I would suggest studying biochemistry or biophysics in during your undergraduate career. Structural determination itself doesn't require too much math and physics as most of the calculations are done by computer programs, but if you want to design novel methods of protein structure determination, you definitely need a strong background in math and physics as well as in biology, biochemistry, and chemistry.

 

As a structural biologist, my research does not just consist of finding protein structures. I do a lot of work relating the structure of my proteins to their biological function, so you could essentially be doing the work of a molecular biologist, only using structural biology as a tool to enhance your understanding of various biological mechanisms.

 

Here's a good page with many links to resources on structural biology:

 

http://www.biochemweb.org/structural.shtml

 

Researching how proteins fold would definitely require a strong background in physics, math, and computer science. Many people studying protein folding are computational biologists, meaning they write computer programs to simulate biological phenomena such as protein folding.

 

Creating a synthetic protein/enzyme is a part of a field called synthetic biology and it is a newly emerging field of research. Synthetic biology is not constrained to industry and there are a few researching synthetic biology in the academia. I remember reading a very interesting article in Science where researchers converted a ribose -binding protein, with no catalytic activity, into a triose phosphate isomerase (an important enzyme in glycolysis/gluconeogenesis). Here's the citation for the article:

 

Dwyer et al., Computational Design of a Biologically Active Enzyme, Science 2004 304: 1967-1971

 

For more information on synthetic biology, you can chek out this MIT site which can direct you to more resources on synthetic biology:

 

http://openwetware.mit.edu/index.php?title=Synthetic_Biology

[scientistsahai]

Ygg well I have a query too!!.

 

I am a bioinformatician and wanna pursue my PhD in structural proteomics.Can u give me the good areas where such kinda R&D is going on?

I have studied chemistry at undergrad, e-business & bioinformatics at masters. What is the best possible way I can enter a Phd prog in UCLA,UCSD etc.

Is in silico studies on proteins going on in any research labs around the world that u r aware of ?

[Etacude]

Unlike first protein crystal structure which took 30 years to resolve, nowadays there computers abound to help resolve these structures. One difficult part is to prepare protein crystals, they may take weeks to crystallise.

 

Another approach to do protein strucutral determination is to do computational modelling and molecular simulations. Basically, the experimentallist prepared and resolved a complex protein structure. You then use this as a basis to run a simulation to investigate the structural behaviour down to individual atoms. Doing this sort of simulations often require supercomputers. Hence, you have chance to access state-of-the-art computers and at the same time carry out many structural analysis which frequently not accessible experimentally.

[donkey]

thanks a lot for your replies - i appreciate it. Very interesting and I've downloaded that Science paper Yggdrasil mentioned. I really like the sounds of this computational stuff but alas it might be too mathematical/computer science based for me. I'm pretty good with computers but I originally chose to do chemistry and not computer science (unlike my twin brother) so that i could get away from maths & programming.

 

I'm certainly going to look into synthetic biology anyway. I've got 1 year of my undergraduate Biochemistry degree left but next year I'll be taking a year out to go on an industrial placement. After that i'll be in my final year and will hopefully have more of an idea what sort of area I want to go into

[Yggdrasil]

Ygg well I have a query too!!.

 

I am a bioinformatician and wanna pursue my PhD in structural proteomics.Can u give me the good areas where such kinda R&D is going on?

I have studied chemistry at undergrad' date=' e-business & bioinformatics at masters. What is the best possible way I can enter a Phd prog in UCLA,UCSD etc.

Is in silico studies on proteins going on in any research labs around the world that u r aware of ?[/quote']

 

Well, I think UCLA would be a great place for you to pursue your PhD, since we have various labs which work on structural biology and we have a graduate program which integrates structural biology and bioinformatics. I haven't looked into opportunities to study structural biology at other universities, but I'm sure you can find many.

 

donkey, I just remembered there was a pretty interesting article on synthetic biology in Scientific American recently, which can be found here:

 

http://www.sciam.com/article.cfm?chanID=sa006&colID=30&articleID=0001D831-41CB-1237-81CB83414B7FFE9F

[donkey]

donkey' date=' I just remembered there was a pretty interesting article on synthetic biology in [i']Scientific American[/i] recently, which can be found here:

 

http://www.sciam.com/article.cfm?chanID=sa006&colID=30&articleID=0001D831-41CB-1237-81CB83414B7FFE9F

you're a star

[Skye]

Another thing you might want to look at is designing analogues of the active sites of enzymes. This doesn't involve a protein, but rather a fairly simple carbon compound (and sometimes metals) that mimics the active site of the protein. These are used a fair in reseach because they are easier to make, often easier to study (it especially makes spectros simpler) and have a fair bit of commercial potential.

[donkey]

Skye, i'm definately interested in that - particularly for structure based drug design sorts of things.

 

after reading up a bit on synthetic biology it appears that the term is pretty broad ranging.

 

What really interests me is the possibility of using elegant biological-style solutions to do funky chemistry /pharmacology (i.e. program DNA to tailor an enzyme capable of producing a useful chemical or protein). This is the computer scientist in me trying to get out, i want to write the program (engineer DNA), run it (let nature produce the protein via translation) and then benefit from the solution (collect a product etc...)

 

Imagine if we could grow some algae that used the energy from light to produce proteins which created loads of hydrocarbons suitable for fuel and plastics. Shame that'd result in an even bigger hole in the ozone layer >.<

 

Can anyone think of more specific useful search terms for this sort of science or am I best to press on with synthetic biology?

[Yggdrasil]

Well, if you're interested in high-thoroughput drug design and discovery, you can search around in Chemical Genomics. Although right now chemical genomics is mainly looking at "brute force" methods of discovering drugs and protein inhibitiors.

[donkey]

brute force

 

rational drug design is way more fun

[donkey]

If anyone cares, I think the buzz word (err buzz phrase) I was looking for was artificial protein instead of synthetic protein.

 

It turns out that about 2 years ago some researchers designed and build the first artificial protein.

 

http://www.sciencedaily.com/releases/2003/11/031121071356.htm

 

Pretty cool