klenchin at REMOVE_TO_REPLY.facstaff.wisc.edu (Dima Klenchin) wrote:
>"deodiaus" <deodiausNOSPAM at gnu.ai.mitNOSPAM.edu> wrote:
>:All the CPU throughput won't help if you don't first solve the mathematics
>:correctly.
Ever heard of numerics?
[...]
>: I am trying to understand how to tackle this protein folding problem.
>:Does anyone know of any good resources about how to solve the problem from
>:first principles. I have read people's papers on methods based on
>:sophisticated computational dynamics, but those avoid the approach I was
>:looking for.
>>The problem, as I see it, is compounded by the fact that many
>protein folds (probably most? - famous RNAse seems to be an
>exception) do not necessarily represent global minimum solution
>(umm, this is not my field so I don't know the "correct term" to
>use but the idea is that they are not in the lowest energetic
>minimum state), just one of those local minima that are deep
>enough for the fold to be "stable".
It is generally asumed that proteins usually do indeed fold to the
global minimum of Gibb's free enthalpy, and this is experimentally
well supported for many of them (though there may be exceptions - but
I'm currently not aware of any).
On the other hand, solving the Schrödinger Equation for a molecule as
complex as a protein is not feasible - it is impossible to solve it
analytically, and numerics get extremely complicated and
time-consuming. I don't think that we'll be able to even solve the
Schrödinger Equation for small peptides in the next decades, so better
not bother about proteins...
>If so, then even if we solve all the math and computer problems
>that exist, we still cannot tell which one of many possible
>folds represents native protein.
This shouldn't be a major problem.
>IMHO, the solution is again
>in experiments, not in paper theory - we need to understand more
>about just how and based on what proteins do fold in the cell.
This is right, though "theoretical experiments", i.e. molecular
calculations, be it classical molecular dynamics or (semi-)quantum
mechanical stuff, are also very useful. Kind of "dialog" between
experiments and theory.
Bye, Frank