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Joined: 09/26/2016
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Hey guys,

Do you have any good books or online courses recommendations? I'm a computer's science guy with only basic chemistry in my formal education (one year university grade chem) and I would like just too much to read or watch videos or whatever about the science behind this. I really want to understand the whole thing of what I'm doing. Any recommendations? My background, well, I have worked a lot with machine learning (MLP mainly and genetic algorithms), I program in C, C++, C#, MSP430 ASM and python but the majority of my work has been in the more commercial areas of the business using more soft skills than hard ones. I'm an amateur microscopist, I have a fairly nice lab for such in my room (yeh my room is bio-hazard lvl 1), I study languages (finishing Japanese right now), I study history, I'm an amateur car mechanic and my formal studies are in electronics. Well, with my background in mind, any suggestions for me to better understand this would be appreciated.

Joined: 10/23/2014
Groups: Contenders

There's a lot of information that can be found by following various links at the top of the home page. However it's somewhat ばらばら.

As a programmer you may be interested looking at the code in recipes or even writing recipes. There is the older GUI programming which is macro-based. The better choice is the LUA language which is a simple easy-to-learn language. The difficulty though is learning the many foldit functions. From fold.it recipe page you can import any recipes into the foldit app. In the app hover over the recipe and you can select edit to view or modify the code. You will want to copy (ctrl-C) and paste the code into something like notepad++ using the LUA language option. The foldit editor is not very good.

Note this is not a weekend project. It's going to take some time and effort.

Joined: 09/24/2012
Groups: Go Science
Hey Skirmitch

Hopefully you'll be addict to this "game".

You might want to start with the Wiki above. Open any recipe in "recipes" above and edit it in an external editor (Notepad etc), you'll quick understand the Lua programming and related Foldit commands.

In my opinion, before to start programming, it's good to play a lot with "hands" in order to see what you would like to automatize with "recipes".

Joined: 09/26/2016
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Heeeey thnks for the answers.

Heeeey thnks for the answers. I think I'll get addicted for sure to the game, I'm 30 and been a gamer for some of those 30 years. Now, regarding my understanding of what I'm doing, what I need goes more to the side, I think, of basic organic chemistry. My doubts right now are so many that would be impractical to ask them individually but just as an example, the kind of questions I have in my mind are of these sorts:

Why does the backbone which, as far as I understand, its just a chain of Cs and Hs can take different shapes (sheets, coils, etc..)?
How do you find where is appropriate a coil or a sheet?
I have seen hydrogen bonds between a side chain and the backbone itself. How is that possible? aren't all the electrons from the backbone already taken by the backbone itself and the sidechains?
Why can I mutate a sidechain??? That sounds like cheating big time, doesn't seem to be the same protein no?
What are the different kind of sidechains for? I'm very curious about this one
I don't think nature chooses sidechains based on "K, I need something hydrophilic and long.... and maybe a bit twisted to the side" like basing in mechanical matters... or does it??
Another of my hobbies is the study of minerals but from the point of view of a collectionist so crystallography is not at all unfamiliar to me but I didn't know it could be applied too to organic chains (proteins), is that what happens in coils and sheets?

Well, those are just samples of my questions, most of which emerged when I faced my first non introductory puzzle and saw the chain straight lying in space and questioned myself "omfg, where to begin". So I think this is more like a lack of organic chemistry knowledge than game mechanics knowledge. So any source of info would be very appreciated (books or online courses or whatever)


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A bit about sidechains

There are different types of puzzles - in some we are trying to *predict* how a certain protein will fold, and in these we can't change the sidechains. We also have *design* puzzles, though, where we are trying to design a brand new protein that does not exist in nature - in this case we can change the sidechains to anything that will help our protein fold up as intended. You can read more about different puzzle types on the "foldit 101" page, under "New Players" on the wiki. http://foldit.wikia.com/wiki/Foldit_Wiki

Nature chooses sidechains by random mutation and natural selection - at every spot in a given protein, every amino acid (every sidechain) will eventually be tried many times by random mutation of the DNA - the amino acids that allow the mutated protein to fold into a similar shape, and function well enough for the organism to reproduce, will be kept, and others will quickly die out. Folding mechanics often make the difference between a viable and a non-viable substitution. Some amino acids can substitute easily for each other - leucine and isoleucine, for example, are close to the same size and both hydrophobic (orange in foldit) so they often substitute for each other. Perhaps a cow will have a leucine at a certain position in a certain protein, while the human version of the same protein has an isoleucine there. You can see the shapes and names of the different amino acids at http://foldit.wikia.com/wiki/Foldit-aas - and which ones like to be in sheets or helixes.

Most proteins in nature have many homologs - similarly shaped proteins with similar but not identical amino acids that have all evolved from some long-distant ancestor. Some amino acids will be the same across all the homologs - these are so important to the shape or function that no substitutions have survived. Others vary a lot among the homologs - these may be on the outside, not touching other sidechains, so they can be almost anything. Still others vary only when their neighbors vary - when one is substituted by a larger sidechain, its neighbor must also be substituted by a smaller one, or else they will clash. By looking for these pairs that always vary together, scientists can often tell which sidechains "contact" (come close to touching) when the protein is folded up.

Joined: 09/26/2016
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Awesome reply, Thnks a lot

Awesome reply, Thnks a lot for the info. I knew the selection process (its where my neural networks and generic algorithms were designed from) but I really didn't know the optimization function was in fact mechanical (shape of the protein once folded), that's very awesome to know. I will chick out that folder 101 yes or yes. Thnks a lot.

Joined: 10/23/2014
Groups: Contenders

I agree with Bruno, it's best to just play the game. I'd suggest playing for a few months to become comfortable using various tools and recipes. There are lot of "hidden" techniques and tricks not obvious at the beginning.

In general there are two ways of approaching foldit puzzles: through biochemistry or like a puzzle. Some of the top players know little about the details of amino acids, sidechains, sheets, helixes, and so on. Foldit does a good job of shielding players from most of the bio details.

I bring this up as early on it's best to learn the tools and techniques skillfully. Learn what recipes to use and when. Much of puzzle design depends not only on what tools or recipes to use but when to use them. How to properly use clashing importance or wiggle power, vitally important topics. How to use Rama Map or Electron Density. Anyway, happy folding!

Joined: 09/26/2016
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Perfect, will check the wiki

Perfect, will check the wiki and keep on folding as I have been then more puzzle oriented. After that I'll go deeper into chemistry.


Developed by: UW Center for Game Science, UW Institute for Protein Design, Northeastern University, Vanderbilt University Meiler Lab, UC Davis
Supported by: DARPA, NSF, NIH, HHMI, Amazon, Microsoft, Adobe, Boehringer Ingelheim, RosettaCommons