Tables for
Volume F
Crystallography of biological macromolecules
Edited by M. G. Rossmann and E. Arnold

International Tables for Crystallography (2006). Vol. F. ch. 21.1, p. 503   | 1 | 2 |

Section Contacts and environments

G. J. Kleywegta*

aDepartment of Cell and Molecular Biology, Uppsala University, Biomedical Centre, Box 596, SE-751 24 Uppsala, Sweden
Correspondence e-mail: Contacts and environments

| top | pdf |

Hydrophobic, electrostatic and hydrogen-bonding interactions are the main stabilizing forces of protein structure. This leads to packing arrangements where hydrophobic residues tend to interact with each other, where charged residues tend to be involved in salt links and where hydrophilic residues prefer to interact with each other or to point out into the bulk solvent. Serious model errors will often lead to violations of such simple rules of thumb and introduce non-physical interactions (e.g. a charged arginine residue located inside a hydrophobic pocket; Kleywegt et al., 1996[link]) that serve as good indicators of model errors. Directional atomic contact analysis (Vriend & Sander, 1993[link]) is a method in which these empirical notions have been formalized through database analysis. For every group of atoms in a protein, it yields a score which in essence expresses how `comfortable' that group is in its environment in the model under scrutiny (compared with the expectations derived from the database). If a region in a model (or the entire model) has consistently low scores, this is a very strong indication of model errors. The ERRAT program is based on the same principle, but it is less specific in that it assesses only six types of non-bonded interactions (CC, CN, CO, NN, NO and OO; Colovos & Yeates, 1993[link]).

Hydrogen-bonding analysis can often be used to determine the correct orientation of asparagine, glutamine and histidine residues (McDonald & Thornton, 1995[link]). Similarly, an investigation of unsatisfied hydrogen-bonding potential can be used for validation purposes (Hooft et al., 1996b[link]), as can calculation of hydrogen-bonding energies (Morris et al., 1992[link]; Laskowski, MacArthur et al., 1993[link]).

Finally, a model should not contain unusually short non-bonded contacts. Although most refinement programs will restrain atoms from approaching one another too closely, if any serious violations remain they are worth investigating, since they may signal an underlying problem (e.g. erroneous omission of a disulfide restraint or incorrect side-chain assignment).


First citation Colovos, C. & Yeates, T. O. (1993). Verification of protein structures: patterns of nonbonded atomic interactions. Protein Sci. 2, 1511–1519.Google Scholar
First citation Hooft, R. W. W., Sander, C. & Vriend, G. (1996b). Positioning hydrogen atoms by optimizing hydrogen-bond networks in protein structures. Proteins Struct. Funct. Genet. 26, 363–376.Google Scholar
First citation Kleywegt, G. J., Hoier, H. & Jones, T. A. (1996). A re-evaluation of the crystal structure of chloromuconate cycloisomerase. Acta Cryst. D52, 858–863.Google Scholar
First citation Laskowski, R. A., MacArthur, M. W., Moss, D. S. & Thornton, J. M. (1993). PROCHECK: a program to check the stereochemical quality of protein structures. J. Appl. Cryst. 26, 283–291.Google Scholar
First citation McDonald, I. K. & Thornton, J. M. (1995). The application of hydrogen bonding analysis in X-ray crystallography to help orientate asparagine, glutamine and histidine side chains. Protein Eng. 8, 217–224.Google Scholar
First citation Morris, A. L., MacArthur, M. W., Hutchinson, E. G. & Thornton, J. M. (1992). Stereochemical quality of protein structure coordinates. Proteins Struct. Funct. Genet. 12, 345–364.Google Scholar
First citation Vriend, G. & Sander, C. (1993). Quality control of protein models: directional atomic contact analysis. J. Appl. Cryst. 26, 47–60.Google Scholar

to end of page
to top of page