SIGNIFICANCE OF STRUCTURAL-CHANGES IN PROTEINS - EXPECTED ERRORS IN REFINED PROTEIN STRUCTURES

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.