Structure validation by Cα geometry: ϕ,ψ and Cβ deviation

Abstract

Geometrical validation around the Calpha is described, with a new Cbeta measure and updated Ramachandran plot. Deviation of the observed Cbeta atom from ideal position provides a single measure encapsulating the major structure-validation information contained in bond angle distortions. Cbeta deviation is sensitive to incompatibilities between sidechain and backbone caused by misfit conformations or inappropriate refinement restraints. A new phi,psi plot using density-dependent smoothing for 81,234 non-Gly, non-Pro, and non-prePro residues with B < 30 from 500 high-resolution 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 gamma-turn conformation near +75 degrees,-60 degrees, counted as forbidden by common structure-validation programs; however, it occurs in well-ordered parts of good structures, it is overrepresented near functional sites, and strain is partly compensated by the gamma-turn H-bond. Favored and allowed phi,psi regions are also defined for Pro, pre-Pro, and Gly (important because Gly phi,psi angles are more permissive but less accurately determined). Details of these accurate empirical distributions are poorly predicted by previous theoretical calculations, including a region left of alpha-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. [Proteins 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).

Implementation of the SCC-DFTB Method for Hybrid QM/MM Simulations within the Amber Molecular Dynamics Package

“…Lovell et al results 86 agree very well with the prediction from the QM trajectories displayed in Figure 5.…”

GacA is essential for Group A Streptococcus and defines a new class of monomeric dTDP‐4‐dehydrorhamnose reductases (RmlD)

“…The final model was refined to 1.1 Å resolution with an R factor of 12.9% and R free of 15.5%. The Ramachandran plot revealed that 98% of all residues are in favored regions, with no outliers as calculated by MolProbity (Lovell et al ., 2003). The co‐ordinates and structure factors have been deposited with the RCSB Protein Data Bank with PDB ID code 4WPG.…”

Unfolding, Aggregation, and Amyloid Formation by the Tetramerization Domain from Mutant p53 Associated with Lung Cancer

“…Instead, we used limiting assumptions by constraining the backbone dihedral angles of the substituted Val334 residue into two idealized, energetically favorable conformations. The first was the left-handed α-helix (57°, 47°), which is the closest minimum in the Ramachandran plot (44) Figure 8A, where the distorted portion of the minimized structure is superimposed on the wild-type crystal structure. As seen in the companion Figure 8B, the Val334 side chain extends freely on the surface of the protein, where it is predominantly exposed to the solvent.…”