Hi Andrew.
>    I was wondering what scripts are typically used when you are  
> close to
> finishing the structure calculation.  I am currently using  
> refine.py and it
> outputs an ave.pdb file.   I also have found a non-python script
> average.inpin analyze_sry folder in eginput of the xplor-nih main
> folder.  I am looking for a protocol or method for determining the  
> final set of
> structures when you are very close.
The script refine.py is pretty much what you want, I think. The  
protocol should give you converged structures with good (maximal)  
satisfaction of the experimental data. A lot of people would follow  
the initial fold-determination with refinement in solvent nowadays,  
but you don't need to.
> Also, how many structures are typically done in the final structure
> calculation? 100? 200?  Of that what percent is acceptable to  
> submit as a
> final cluster 20%, 10%?
This is an open question as far as I know. There are some (NMR- 
determined) PDB entries that are single-conformer! The idea of an  
"NMR ensemble" is mostly to illustrate the self-consistency  
(precision) of the calculation. The most interesting issue is the  
accuracy of the ensemble, however, and there is no general way to  
assess structural accuracy. That's why the level of compliance with  
target covalent geometries (like Ramachandran stats) are almost  
always reported (although this practice is not satisfactory in my  
opinion).

To "really determine" an NMR structure, the initial coordinates  
should be an extended conformation, or some other unfolded  
conformation (say, uncommenting the protocol.genExtendedStructure()  
line in refine.py). 20% convergence in a calculation like that would  
be pretty good, I think, so if 20 of 100 structures were low energy  
and self-consistent, you could publish them. If you're getting a much  
smaller number of converged structures, you could tune the  
calculation protocol to increase the amount of convergence, anyways.  
Making the hot phase longer, or hotter, or making the cooling phase  
longer, or slower, often changes the observed level of convergence.  
The arguments to simulationTools.StructureLoop() like  
"averageTopFraction" or "averageTopNum" allow you to adjust how many  
of the structures are considered acceptable.

Simulated annealing is a method for minimizing a multidimensional  
target function, not a model of a real physical process, so there is  
no general relationship between NOEs and the precision of an  
ensemble. This is true even under a valid assumption of a single- 
conformer interpretation of the NOEs. This concept is elegantly  
demonstrated in  "Conformational variability of solution nuclear  
magnetic resonance structures." J. Mol. Biol. 250, 80-93 (1995). I  
think the "information content" of a given fold's topology is a major  
piece of the puzzle, as investigated in "Quantitative evaluation of  
experimental NMR restraints." J. Am. Chem. Soc. 125, 12026-12034  
(2003); you may want to try the QUEEN software (http:// 
www.cmbi.kun.nl/software/queen/) to feel/look more convinced of your  
structure's self-consistency.

I hope that helps a bit,

Ryan

Ryan M.B. Hoffman
PhD Candidate (lab of Brian D. Sykes)
Department of Biochemistry,
University of Alberta.
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