H. A. Hauptman and D. A. Langs
Hauptman-Woodward Medical Research Institute & Department of
Structural Biology
SUNY at Buffalo, 73 High Street, Buffalo, NY
14203-1196
Abstract:
The
crystallographic phase problem is formulated as a problem in constrained
global minimization. In contrast to traditional direct-methods
techniques using X-ray diffraction, this formulation does not require
that the density function be positive everywhere. Instead, suitable
generalization of the well known Shake-and-Bake formalism, here
called Neutron Shake-and-Bake, exploits prior knowledge that the
density function, as called for in the neutron diffraction case, is now
permitted to assume negative, as well as positive, values. The initial
application is made to the solution by Neutron Shake-and-Bake of
the 199 atom (113 hydrogen atoms plus 86 nonhydrogen atoms) cyclosporin
structure using experimental neutron diffraction data alone. Comparing
the relative ease of this structure determination with the far greater
challenge posed by the deuterated cyclosporin isomorph, in which the
density function is positive everywhere, shows that, in sharp contrast
to the prevailing view, the positivity of the density function not only
does not facilitate, but actually substantially hinders, the phase
determination process.
This research was supported by NIH grant EB002057.
2008 Run
Nov 19th - Dec 22nd
