A SELF-VALIDATION TECHNIQUE FOR PROTEIN-STRUCTURE REFINEMENT - THE EXTENDED HAMILTON TEST

An extension is proposed for the self-validation Hamilton test [Hamilt on (1965). Acta Cryst. 18, 502-510] for crystallographic refinement. T he method is based on the statistical F test and evaluates the signifi cance of the R-factor ratio between two refinement protocols. The gene ral case of two refinements carried out with different numbers and typ es of non-linear restraints is examined. The restraints are considered as extra observations weighted by a coefficient expressing their effe ctive number. There exists a restriction on the weighting coefficients between the two refinements. An empirical method to evaluate the effe ctive number of restraints is provided. The method may allow the detec tion of unreasonably tight restraints. The expectation value for r.m.s . R(free), given the r.m.s. R, can be estimated. Thus, the significanc e of the observed drop in R(free), can be assessed. Compared to cross- validation using R(free) [Brunger (1992). Nature (London), 355, 472-47 4] self-validation has the advantage that it does not require omission of any experimental data. The significance of the improvement obtaine d by moving from isotropic to anisotropic description of thermal param eters in the refinement of a protein at 1.5 Angstrom resolution is use d as an example.