Rm. Stroud et Eb. Fauman, SIGNIFICANCE OF STRUCTURAL-CHANGES IN PROTEINS - EXPECTED ERRORS IN REFINED PROTEIN STRUCTURES, Protein science, 4(11), 1995, pp. 2392-2404
A quantitative expression key to evaluating significant structural dif
ferences or induced shifts between any two protein structures is deriv
ed. Because crystallography leads to reports of a single (or sometimes
dual) position for each atom, the significance of any structural chan
ge based on comparison of two structures depends critically on knowing
the expected precision of each median atomic position reported, and o
n extracting it for each atom, from the information provided in the Pr
otein Data Bank and in the publication. The differences between struct
ures of protein molecules that should be identical, and that are norma
lly distributed, indicating that they are not affected by crystal cont
acts, were analyzed with respect to many potential indicators of struc
ture precision, so as to extract, essentially by ''machine learning''
principles, a generally applicable expression involving the highest co
rrelates. Eighteen refined crystal structures from the Protein Data Ba
nk, in which there are multiple molecules in the crystallographic asym
metric unit, were selected and compared. The thermal B factor, the con
nectivity of the atom, and the ratio of the number of reflections to t
he number of atoms used in refinement correlate best with the magnitud
e of the positional differences between regions of the structures that
otherwise would be expected to be the same. These results are embodie
d in a six-parameter equation that can be applied to any crystallograp
hically refined structure to estimate the expected uncertainty in posi
tion of each atom. Structure change in a macromolecule can thus be ref
erenced to the expected uncertainty in atomic position as reflected in
the variance between otherwise identical structures with the observed
values of correlated parameters.