Re: [DIYbio] Re: Medicine Simulation Newbie

Super nice idea to circularise proteins/enzymes -> more heat stable !

On Thu, Nov 27, 2014 at 10:00 PM, Dan <djwrister@gmail.com> wrote:
> If you are looking for an interesting protein modeler, here is the winner of
> iGEM undergrad this year. Amazing project that circularizes proteins,
> provides a tool to allow you to design and do it yourself and provides lots
> of computing power to do so.
>
> http://2014.igem.org/Team:Heidelberg
>
>
>
> On Nov 27, 2014, at 2:35 PM, Josiah Zayner <josiah.zayner@gmail.com> wrote:
>
> Ujjwal,
>
> I think you are looking at this the wrong way. It is not possible in
> most Scientific endeavours to know all possible outcomes. The key is to ask
> the correct question. If my question is: "Could protein X bind molecule Y?".
> I can come upon a very reasonable conclusion using Molecular Dynamics(MD).
>
> If my questions is "How does protein X work?" That is also something that is
> quite possible to uncover and volumes of work have been published on
> understanding how proteins function through use of Molecular Dynamics(MD)
> which then were verified later by physical experimentation.
>
> I think MD is a very worthwhile endeavour for someone with programming and
> computational skills to contribute to Science. I do simulations myself.
>
>
> On Thu, Nov 27, 2014 at 12:22 PM, Ujjwal Thaakar <ujjwalthaakar@gmail.com>
> wrote:
>>
>> Hi Josiah,
>> Mine was a really abstract question. I basically wanted to get a feel of
>> how productive it is right now to design molecular machinery with
>> preciseness of behaviour through computational biology. I understand I may
>> not be making complete sense to you due to my lack of understanding of the
>> material involved at this point of time. Believe me you're not making much
>> sense to me either :p
>> Thanks for the pointers though. I do get a feel that while it can be done
>> for small sample sizes and certain conditions, it's yet not possible or even
>> computationally feasible to model out a protein's structural folding and
>> interactions for every possible configuration.
>>
>> On Fri Nov 28 2014 at 01:42:04 Josiah Zayner <josiah.zayner@gmail.com>
>> wrote:
>>>
>>> I think your question is a complicated one. What do you mean by accuracy?
>>>
>>> People have "accurately" folded small proteins using simulations as
>>> measured by the Root Mean Square Deviation(RMSD) between the backbone(C
>>> alpha I think) of the two structures. But still, what do you mean by
>>> accurate? A 1 angstrom RMSD? A 0.5 angstrom RMSD? &c. How long.often does
>>> the simulation need to sample that state before you view it as significant?
>>> 5 picoseconds? 100 picoseconds?
>>>
>>> Protein function is a thermodynamic problem. There really is no measure
>>> of "accuracy". Proteins are constantly being altered by their
>>> environment(i.e. temperature and solvent) see work by Boltzmann and Gibbs to
>>> start. What this means is that there are a very high number of possible
>>> conformations a protein can undertake. We call this the ensemble.
>>> Theoretically an ensemble contains every possible conformation of the
>>> protein. Most physical measurements we do of proteins are ensemble
>>> measurements. A Molecular Dynamics simulation is a single molecule
>>> equilibrium simulation which can't possibly sample all known states of the
>>> protein. For a single small protein with 100 amino acids and 3 degrees of
>>> freedom for each backbone phi psi angle you are talking 3^198 (This doesn't
>>> include sidechains and is probably a gross underestimate) see
>>> http://en.wikipedia.org/wiki/Levinthal%27s_paradox. There are techniques to
>>> increase the sampling frequency of different states but 3^198 is an awful
>>> lot. Your CPU clock frequency is probably 3^9 / second which means is would
>>> take about 9^86 years just to count that high without doing any other
>>> calculations.
>>>
>>> I think the question you might be trying to ask is "Can simulations
>>> predict protein function or binding to other molecules?" The answer to that
>>> is "Sometimes". It really depends on the thermodynamics of the protein in
>>> question and the difficulty in sampling the state you are attempting to
>>> understand.
>>>
>>> I don't know what you mean by "different environments". Different
>>> solvents? With other molecules? In a membrane? All of the above?
>>>
>>>
>>>
>>> Josiah Zayner
>>>
>>>
>>> On Thu, Nov 27, 2014 at 11:47 AM, Ujjwal Thaakar
>>> <ujjwalthaakar@gmail.com> wrote:
>>>>
>>>> To what level of simulation accuracy has computational biology reached?
>>>> To what degree of accuracy can we predict the behaviour of molecules in
>>>> different environments?
>>>>
>>>>
>>>> On Wednesday, November 26, 2014 4:56:47 AM UTC+5:30, Josiah Zayner
>>>> wrote:
>>>>>
>>>>> I think first you need to understand some basic biochemistry before you
>>>>> begin.
>>>>> Unless you are trying to simulate disease spread. Numerous people have
>>>>> worked on this and articles and methods should be easy to find.
>>>>>
>>>>> If you are trying to understand how drugs help prevent or cure diseases
>>>>> such as Ebola you need to look at the proteins. Here is a tutorial for that:
>>>>> https://docs.google.com/document/d/13H-d8TzDn3m1H2BE_RA617H7g7dBjz_yibCLhLDejSQ/
>>>>> which can be followed up with simulating the proteins which can be
>>>>> achieved with a tutorial like this:
>>>>> http://web.mit.edu/vmd_v1.9.1/namd-tutorial-unix.pdf
>>>>>
>>>>>
>>>>> On Tuesday, November 25, 2014 5:58:38 AM UTC-8, Gokula Krishna wrote:
>>>>>>
>>>>>> Hello There,
>>>>>>
>>>>>> I am a Computer Science Engineer who is interested in simulating
>>>>>> vaccines for various disease. Can anyone help me out on how to proceed? I
>>>>>> have searched for various journals regarding this, but it is subtle to grasp
>>>>>> and they are too abstract.
>>>>>>
>>>>>> This is the basic thesis that I have regarding the program:
>>>>>> 1-> The user should specify the disease the various properties about
>>>>>> the disease and environment.
>>>>>> 2-> The program tests whether the given disease is curable for the
>>>>>> vaccine.
>>>>>> 3-> What are the parameters should I consider?
>>>>>>
>>>>>> Can you suggest me a good place to start with?
>>>>>>
>>>>>> Thanks in advance.
>>>>
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--
----------------------------------------
Brian Degger
twitter: @drbrian

http://makerspace.org.uk
http://transitlab.org
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