Section 21.2.2.2.1. Validation of stereochemical and non-bonded parameters

Morris et al. (1992) pioneered this type of validation for proteins. The software PROCHECK (Laskowski et al., 1993), which implements and extends this approach, is described in detail in Chapter 25.2 of this volume. A very important evaluation criterion is the Ramachandran-plot quality, where the distribution of the backbone φ, ψ angles of a given protein structure is compared to that in high-quality structures. The comparison is performed both globally, by determining the proportion of the residues in favourable (core) regions of the plot, and locally, by the log-odds (G-factor) value, which measures how normal or unusual a residue's location is in the plot for a given residue type.

A similar strategy is used to evaluate other stereochemical parameters, such as the side-chain torsion angles (, , etc.), the peptide bond torsion (ω), the C^α tetrahedral distortion, disulfide bond geometry and stereochemistry.

An evaluation of the backbone hydrogen-bonding energy is also performed, using the Kabsch & Sander (1983) algorithm, by comparison with distributions computed from high-resolution protein structures.

Other programs like WHAT IF (Hooft, Vriend et al., 1996) perform similar evaluations. This program computes the expected φ, ψ distribution for each residue type from a data set of non-redundant high-quality structures and evaluates how the φ, ψ distribution of a given protein deviates from the expected values (Hooft et al., 1997). A somewhat different version of this approach is proposed by Kleywegt & Jones (1996). WHAT IF also computes other quality indicators such as the number of buried unsatisfied hydrogen bonds or the extent of the overlap of van der Waals spheres (`clashes'). In addition, it verifies the orientation of His, Gln and Asn side chains, based on a hydrogen-bond network analysis, which also takes into account hydrogen bonds between symmetry-related molecules (Hooft, Sander & Vriend, 1996).

The very small fraction of structures (< 1.3%) for which only the C^α coordinates are deposited cannot be validated by the standard techniques. For these structures, two sets of parameters were shown to be useful (Kleywegt & Jones, 1996). They are the C^α—C^α distances and a Ramachandran-like plot which displays for each residue the dihedral angle against the angle. Deviations from the expected distributions of these parameters, computed from a set of high-quality complete protein structures, are used as quality indicators.

The validation of nucleic acid stereochemistry, in particular DNA, has a much shorter history. Only in recent years has the number of high-quality nucleic acid crystal structures become large enough to permit the derivation of reliable conformational trends. Schneider et al. (1997) derived ranges and mean values for the torsion angles of the sugar–phosphate backbone in helical DNA from a set of 96 oligodeoxynucleotide crystal structures. These ranges form the basis for the nucleic acid structure validation protocols currently implemented at the NDB.