[sdpd] Re: SDPD stagnation

[Gregory A Stephenson <STEPHENSON_GREGORY_A...@LILLY.COM>]

I believe that we will see a continued increase in SDPD for organic molecules,
since the problem can often be restrained to a meaningful low number of
degrees of freedom and with the improvements made in the molecular searching
methods.  The molecules are of typically well defined chemical composition,
established through chemical data established by Mass Spectrometry and NMR
typically and most molecular fragments can be treated as rigid bodies (thanks
to covalent bonds and common fragment conformations).  The major hurdles have
been cleared by the researchers who have developed the algorithms (hats off to
Shankland, David, Harris and appologies for the many omissions).  A major
benefit of the newer commercial GUI's is the ability to readily create the
rigid bodies for the relatively large organic molecules (lots of atoms and
numbers to input in non user friendly GUI).  From what I have seen, indexation
plays a similar role in organic crystal structure determinations by single
crystal or powder diffraction, in that it is the pivotal step.  If it can be
indexed, I can usually get a good enough data set to solve the problem.  The
uncertainty associated with indexation, and space group assignment, in
addition to assumptions made in imposing restraints on the problem limits the
success rate one can expect.  It may take numerous iterations to solve the
problem.  For that reason, the impact of the GUI is that it reduces the
up-front time expenditure so that one has not spent more time setting up to
solve the problem than would have been spent in potentially growing single
crystals.  From what I am seeing, the SDPD approach is going to hold a
limited, albeit useful, niche in crystallography.  Those incredibly small
crystals that I can not get large enough for single crystals determination
using a synchrotrons or low quality crystals (sometimes twins-although single
crystal area detectors are closing this gap).  Protein crystallographers would
very likely be happy with the SDPD results, but once you have become
accustomed to high res single crystal data on small molecules the quest for
these results may be reserved for instances where we are hard up for
structural information and have exhausted the alternatives.