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The science of [email protected]

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The problem you're focusing on, at [email protected], is the prediction of protein structures from their amino acid sequences almost all human diseases are caused by mutations in proteins that affect their three dimensional structures and functions and so if we can reliably predict protein structures we could understand how mutations cause disease and from there perhaps go on to develop therapies I'm working on trying to design inmmunogens that will elicit antibodies against the HIV so are a critical part of a vaccine Design proteins that will present that piece of HIV in just the right conformation so that protein, once it's taken off a computer and turned into a real physical protein that's put into a person's blood will cause that person to make antibodies against the epitope of HIV up until recently, it has been pretty much thought impossible to reliably predict the structure of proteins from their sequences Instead, protein structures are currently determined using time consuming and expensive experiments which can only be applied to a small subset of proteins if instead we could accurately and reliably predict protein structures it would revolutionize much of molecular biology To carry out this work, we've developed a computer program called Rosetta Success in our work would have broad ranging implications for human health ranging from the development of a vaccine for HIV to the eradication of Malaria The sequence of amino acids that make up proteins is directly determined from the genetic code otherwise known as the sequence of molecules in DNA DNA, like proteins, is also made of molecular sub-units with specific properties Withing the nucleus a kind of imprint of DNA is transcribed into a similar molecule called RNA carrier molecules transport amino acids to an enormous structure called the ribosome The ribosome translates the information in RNA into a chain of amino acids You know, think about putting a rope in a box with no gravity and think about how many different ways this rope could actually fall in that box So you know the number of combinations, the number of possibilities, are pretty much astronomical A strand of amino acids, the order of which has been determined by the genetic code can indeed be thought of as rope or chain-like However, the properties of the links, in this case amino acids cause portions of the chain to be attracted to or repelled from each other As well as elements in the cellular environment What the Rosetta program does, is calculate the likehood of these interactions between segnments of the chain based upon favourable energy levels The most likely 3D structure of the chain will take the least amount of free energy to fold So last summer I started modifying Rosetta to be used with the BOINC distributed computing platform Before BOINC we had around 400 computers that we can run our calculations on locally but now with BOINC we have thousands of computers that we can run our jobs on located all around the globe, and it's really exciting to see how it developed What we're doing at [email protected], is analogous to searching the surface of a large rocky planet for the lowest elevation point Imagine you have a team of human explorers working with you and they're all exploring around the planet The team is small, it is quite likely that no explorer will actually find the lowest elevation point particularly if there are a lot of tall mountains that lead to explorers getting trapped at particular places on the planet Now instead imagine that you have a very large team of explorers and they each parachute down randomly on the surface of the planet and then start searching for the lowest elevation point The more explorers you have the more likely it is that at least one of them will find the lowest elevation point of the planet Now on [email protected], we're instead searching the energy landscape for a protein trying to find the lowest energy structure for the amino acid sequence The more computers there are doing these searches the more likely it is that somebody will actually find it In each step of the Rosetta search process a move is made in which part of the protein structure is randomly altered The top left panel of the screen saver shows each move as it is being made If Rosetta calculates that the energy has decreased with the move it is accepted and displayed in the middle panel The lowest energy structure found so far is displayed in the next panel over Shown below this is the actual shape of the protein, if it is known The panel to the right tracks how closely each accepted move compares to the known protein structure The bottom panel tracks the energy of each move The energy after the most recent move is located on the right In the bottom right corner is a graph which plots the energy versus how close the shape is to the actual protein From this graphic you can tell when your search has entered a new region of the energy landscape So one of the dreams of many people on this project is that out of the - say millions users - on [email protected] there is going to be some, maybe some kids, some 9 years old girls in Korea who grow up looking at these fascinating proteins on their screens and develop a very strong intuition for what molecules do and they're going to grow up and become great biophysicists and because of this intuition that developed when they were young they will be able to solve the problem immediately This is a whole new step forward in the relationship between scientists and the public To solve the problem of protein structure prediction It's quite clear that it's really not possible without the contributions of people from all over the world like yourselves because it's such a big computing problem that it just cannot be done with any in-house resources so we can only do it collaboratively as a collaboration between us and you and through this collaboration we can solve a problem which I really think couldn't be solved otherwise

Video Details

Duration: 7 minutes
Country: United States
Language: English
Views: 272
Posted by: southseeker on May 23, 2009

Explains the science behind top research on protein folding at the University of Washington's Baker Lab. 3D animations and interviews. For more info: http://boinc.bakerlab.org/rosetta/

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