Structure Validation by C Geometry: , and C Deviation

Abstract

Geometrical validation around the C is described, with a new C measure and up- dated Ramachandran plot. Deviation of the ob- served C atom from ideal position provides a single measure encapsulating the major structure-valida- tion information contained in bond angle distor- tions. C deviation is sensitive to incompatibilities between sidechain and backbone caused by misfit conformations or inappropriate refinement re- straints. A new , plot using density-dependent smoothing for 81,234 non-Gly, non-Pro, and non- prePro residues with B < 30 from 500 high-resolu- tion proteins shows sharp boundaries at critical edges and clear delineation between large empty areas and regions that are allowed but disfavored. One such region is the -turn conformation near 75°,60°, counted as forbidden by common struc- ture-validation programs; however, it occurs in well- ordered parts of good structures, it is overrepre- sented near functional sites, and strain is partly compensated by the -turn H-bond. Favored and allowed , regions are also defined for Pro, pre- Pro, and Gly (important because Gly , angles are more permissive but less accurately determined). Details of these accurate empirical distributions are poorly predicted by previous theoretical calcula- tions, including a region left of -helix, which rates as favorable in energy yet rarely occurs. A proposed factor explaining this discrepancy is that crowding of the two-peptide NHs permits donating only a single H-bond. New calculations by Hu et al. (Pro- teins 2002 (this issue)) for Ala and Gly dipeptides, using mixed quantum mechanics and molecular mechanics, fit our nonrepetitive data in excellent detail. To run our geometrical evaluations on a user-uploaded file, see MOLPROBITY (http://kinemage. biochem.duke.edu) or RAMPAGE (http://www-cryst. bioc.cam.ac.uk/rampage). Proteins 2003;50:437- 450.