Hi, Tim, When we were working on our paper in 2011, refmac had a bug that always indicated in depostions that riding hydrogens were used, whether they were or not. Published methods did not always clarify this issue. Since we could not be definitive, we refrained from saying too much about it. However, then current refmac structures did have plenty of close non-bonded contacts as all-atom models, even though some (most? all?) of them were refined with riding hydrogens 'on'. We should look again with a recent sample of structures and find out.
Your point is well taken that constrained hydrogen coordinates may not agree well where accurate data is available for hydrogen positions. One builds the best model that one can with the available data. PrimeX is intended for use with moderate resolution X-ray structures. Hydrogen positions are determined by the force field while heavier atom positions are refined to agree with the diffraction data and force field. Cheers, Jeff On Monday, June 16, 2014 7:14 AM, Tim Gruene <t...@shelx.uni-ac.gwdg.de> wrote: 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
