Dear Jeff,
I would assume that clashing hydrogen atoms beome less and less an issue
with current refinement programs, since those I am familiar with
(refmac5 and phenix) both genereate constrained hydrogen atoms by
default now, and it has been like this for quite some time - so the
situation should become better for modellers.
You may also want to note that constrained hydrogen positions are a
crude approximation and only work with X-ray data where hydrogen atoms
have little impact on the data. Our comparison between hydrogen
restraints and constraints (http://dx.doi.org/10.1107/S1600576713027659)
report the greater quality of restraints vs. constraints when it comes
to neutron data, where hydrogen atoms do matter. Hydrogen positions are
much more flexible than the usual riding atom model may imply. This may
affect in silico simulations.
Best,
Tim
On 06/16/2014 04:34 AM, Jeffrey Bell wrote:
> Hi, all,
>
> I am glad to see these matters being discussed. I think we all believe that protein crystallographers should be concerned with producing models that modelers and chemists can respect and use.
>
> Schrödinger spends a lot of time thinking about ligands; its refinement program, PrimeX, has a very simple way of handling ligand issues. All that a crystallographer has to do is get the charge and bond order right, and the force field then automatically does atom typing and generates all restraints.
>
>
> However, use of our cif library files brings up another matter that must be understood first. Use of PrimeX, even at low resolution, involves refinement of all hydrogen atom positions. The Richardsons have abundantly demonstrated how important hydrogen coordinates are to accurate model building.
>
> This matter of hydrogen coordinate refinement is closely connected to the editorial that started this thread. Computational chemistry in drug discovery, and elsewhere, uses all-atom models. When you add hydrogen atoms to most models in the PDB, many chemically-impossible overlaps of atoms result (see Acta Cryst. 2012, D68, 935-952 for more information; ask me for a copy). This issue is almost as much of an annoyance for computational chemists as bad ligand geometry because they see it in almost every structure.
>
> If anyone would like to try PrimeX, either for ligand restraint generation or refinement, please let me know. Schrödinger offers academic institutions one year of free access, which may be renewed on a case-by-case basis. Crystallographers at companies will also qualify for a free evaluation trial.
>
>
> Cheers,
>
> Jeff Bell
> PrimeX developer
> Schrödinger, Inc.
>
--
Dr Tim Gruene
Institut fuer anorganische Chemie
Tammannstr. 4
D-37077 Goettingen
GPG Key ID = A46BEE1A
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