Re: [DIYbio] Re: Protein Categorization

I'm not talking about folding proteins based on a magic id, I'm trying to classify known folds with unique id's.  A logarithmic scale can be defined with integers easily (e.g. 14/64 gets you to a precision of 0.21875 on a linear scale alone with only 6 bits, so for every 0.21875 pH difference you would be able to have a distinct protein defined with the same sequence and chunk,) it being a logarithmic scale is essentially half of the question I was asking relative to pH.  The other half being what is the step needed for the scaling (e.g. do I need 6 bits or do I need 8 bits to define it at the required precision.)

The chaperone proteins and such I'm not so concerned about because of the chunking parameters - I already know how to get that into a single integer for any protein with a high degree of stability in the conformation (e.g. if you have 2 amino acids in a polypeptide you might start with two rotomers, which would be chunked out as 0 or 1, you don't need to know what the most thermodynamically stable conformation is as derived by the folding process, or even which one is hit by the various chaperones, you only need to know the chunking step size and ambient dimensional parameters such as pH, salinity, dissolved sugars, etc to say "from this starting conformation the most thermodynamically stable state is x and you shouldn't expect to see the next most thermodynamically stable state until the next chunk signifying the next starting conformation given the same ambient dimensional parameters.")

The knowns are:
-folding
-chunking
-sequence

The unknowns are:
-dimensions (pH, sugar, salinity, etc)
-step sizes and scales of those dimensions

The objective here is to get a concise list of dimensions (even if they are completely different from "pH, salinity, dissolved sugar..." and are in the realm of "ambient electronegativity, ambient inclusions with their electronegativity, size, dispersion pattern or fractal geometry...")  Knowing the distinct id is the only aspect involved in this question, the folded conformation is data tied to that id, and while initially derived from it, not expected to be a set of generation routines where you enter the id and have it spit out the completely folded protein with any degree of accuracy - just a form of classification.

On Friday, December 8, 2017 at 12:19:49 PM UTC-5, Skyler Gordon wrote:

Listen,

The cell doesn't just change the pH (which isn't in an integer scale, it has infinite range to it - and on a logarithmic axis), and the protein magically folds correctly. There are hundreds of different cell pathways for processing proteins to get them into a specific shape before being "shuttled" to the proper place.

This is a subject that people spend their entire lives studying, and that is just for a single protein much less every peptide combination possible.

Saying one sequence will fold like another because they are similar polypeptides in similar conditions is like saying two people with similar traits will act the same under the same circumstances or that two apple trees will taste the same since you planted the seeds in the same soil. It's possible, but really unlikely. Just a single difference in CELL PROTEIN PROCESSING will change everything and your program goes out the window.

Now you're talking about having users input their specific cell pathways to try to determine exactly what happens as a sum of those pathways and then GUESSING how all those variables are weighted.

Remember, even if you think you got it right you'll have to use X-ray crystallography to find out if you're right. Old school, and classic, but also very very difficult and time consuming.

-SG

On Fri, Dec 8, 2017 at 9:02 AM Patrik D'haeseleer <pat...@gmail.com> wrote:

The closest I've been able to find (at least as far as I understand what you are asking for) is PSCDB - the Protein Structural Change DataBase, but that one seems heavily focused on structural changes induced by ligand binding, not pH or temperature changes etc.

There are likely also some databases out there with information on what the physiological range is for enzymes or other proteins. But it may not have any info on exactly why they lose their function beyond those parameters - whether it's due to a distinct structural change, or they start to denature, or undergo some other non-structural changes that inhibit their function. 

What I am fairly certain you will NOT find, is a database with a large number of proteins documenting in detail how their structure changes with changes with environmental parameters. There just aren't that many proteins that have been documented to switch between distinct structural conformations. And for those proteins we do know about, the characterization of the parameter space will typically be very coarse, e.g. something like "this protein has conformation X at pH 7, but conformation Y at pH 5 in the presence of Ca+".

Patrik

On Thursday, December 7, 2017 at 7:10:01 PM UTC-8, Cory J. Geesaman wrote:

Does anyone know of a set of categorizations for proteins which provide good coverage of all the observed structural conformations?
Examples of what I'm referring to would be the pH, salinity, temperature, and possibly reducing agent concentrations.

The purpose is to try to classify different stable folded proteins for each set of possible changes, so if for instance there's a hard cutoff at a pH of 3 where lower doesn't do anything, or greater than 100C or more than a 90% saturation of salt, or more than a 2% solution with reducing agents (a specific reducing agent or in general,) etc that would be helpful to know.  Additionally, if there is somewhat of a gradient that would be helpful (e.g. will a protein fold different at a pH of 6, 7, and 8 - and if so are there known transition points?)

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