[gmx-users] NOE restraints and undefined hydrogen atoms, virtual interaction sites

[chris.neale at utoronto.ca]

> There's no a priori reason why a mixture of a united-atom detergent  
> sodium dodecyl sulfate and an all-atom peptide *couldn't* work.  
> Neither is there any reason to suppose they *would* work without  
> evidence that the SDS parameters were developed with this purpose in  
> mind and suitably validated. For that, you'll have to read the paper  
> referred to on the page you footnoted [1], I guess. Your other  
> alternative is looking for an all-atom SDS topology that has been  
> validated, but I've no idea whether one exists.

Do you have any suggestions how one would validate the combination of  
two such force-fields? While generally one could always develop new  
parameters using the same methodology as the existing forcefield, it  
is not obvious how one would do this when combining all-atom and  
united-atom representations.

I see how the basic combination rules, etc. could be validated by  
simulating for example an aqueous protein restrained to one half of  
the simulation box and an SDS micelle restrained to the other half of  
the box in order to ensure no vdw contacts and then compare  
equilibrium properties from this simulation to those of an aqueous  
protein and an SDS micelle in separate simulations.

Further, in some situations one could look at the parameters to see  
the there are no striking differences between similar atom types. This  
would definitely be useful for example when trying to combine an  
all-atom protein forcefield with a united-atom forcefield. However,  
SDS doesn't really have any groups that are similar to and protein  
groups. Further, it is not readily apparent to me how one would even  
extend a protein forcefield using the same methodology to SDS and be  
sure based simply on methodology of generation that they were valid in  
combination since there is so little overlap in actual group types.

Thanks,
Chris.