The effects of the number, precision and accuracy of interproton distance restraints, of direct refinement against nuclear Overhauser enhancement (NOE) intensities and of the description of the non-bonded contacts on the precision and accuracy of a nuclear magnetic resonance (NMR) protein structure determination have been investigated. The model system employed is the 56 residue immunoglobulin G binding domain of streptococcal protein G. This choice was based on the availability of a very high resolution NMR structure (atomic root-mean-square distribution of the ensemble of 60 calculated structures about the mean co-ordinate positions of 0.25 A for the backbone atoms, 0.65 A for all atoms and 0.39 A for all atoms excluding disordered surface side-chains). The experimental NMR data set for this structure determination comprised a total of 1058 experimental restraints of which 854 were approximate interproton distance restraints corresponding to all the structurally useful NOEs observable for this protein. The calculations presented in this paper reveal the following. (1) The number of interproton distance restraints constitutes the single most important determinant of both precision and accuracy. The ensemble precision and accuracy improves significantly as the number of interproton distance restraints is increased to an average of approximately 15 per residue, of which approximately 60% involve unique proton pairs; subsequent additions of interproton distance restraints, however, lead to less dramatic improvements as information redundancy sets in. (2) The ratio of ensemble precision to ensemble accuracy (which ranges from 0.5 to 0.7 for the backbone atoms) is approximately independent both of the number, precision and accuracy of the interproton distance restraints, and of whether the structures are refined against interproton distance restraints or directly against NOE intensities. (3) In an ensemble of structures generated from a large number of loose approximate interproton distance restraints (an average of approximately 15 restraints per residue with approximately 60% involving unique proton pairs), the interproton distance vectors corresponding to the restraints are very well defined with approximately 80% of vectors between unique proton pairs having a standard deviation of < or = 0.1 A. (4) The accuracy of the mean co-ordinates of an ensemble of structures is significantly higher than the average accuracy of the individual structures comprising the ensemble. For an average ensemble precision of > or = 0.6 A, the dependence of the accuracy of the mean co-ordinates on ensemble precision is approximately linear.(ABSTRACT TRUNCATED AT 400 WORDS)