Protein Geometry Database: a flexible engine to explore backbone conformations and their relationships to covalent geometry

Abstract

The backbone bond lengths, bond angles, and planarity of a protein are influenced by the backbone conformation (varphi,Psi), but no tool exists to explore these relationships, leaving this area as a reservoir of untapped information about protein structure and function. The Protein Geometry Database (PGD) enables biologists to easily and flexibly query information about the conformation alone, the backbone geometry alone, and the relationships between them. The capabilities the PGD provides are valuable for assessing the uniqueness of observed conformational or geometric features in protein structure as well as discovering novel features and principles of protein structure. The PGD server is available at http://pgd.science.oregonstate.edu/ and the data and code underlying it are freely available to use and extend.

Figure 1.

An active-site peptide geometry feature discovered using the PGD. (A) Shown is the peptide bond between residues His306 and Asn307 in the 0.90 Å resolution structure of Cu-nitrite reductase [PDB code 2bw4 (21)]. 2F_o–F_c electron density is shown at 6.5 ρ_rms (violet mesh), and a plane is shown for reference. (B) Same as A but showing the peptide bond between residues Ala291 and Phe292. For standard planar peptides such as the one in panel B, all five atoms shown lie in a plane. In contrast, in panel A, the Cα atom of residue i + 1 is highly deviant from the plane defined by the Cα_i, C, O, and N atoms. The electron density indicates that the atoms are all reliably positioned. This peptide bond is 37° from planar (ω = 143°). His306 ligates the Cu²⁺, so this is an important structure-function feature that was overlooked. This example is not unique; residues with unrecognized yet real and important deviations in peptide geometry are relatively common.

Figure 2.

Extent and diversity of the database. The residue population of the PGD is shown as a function of resolution (A), amino-acid composition (B), and secondary-structure type (C). The population as a function of resolution is cumulative. At 1.0 Å resolution or better, the current PGD version contains 30 256 residues. Secondary-structure types are defined as follows: ‘H’ — α-helix; ‘G’ — 3₁₀ helix; ‘E’ — β-strand; ‘T’ — hydrogen-bonded turn; ‘S’ — non-hydrogen-bonded turn; ‘I’ — π-helix; and ‘B’ — β-bridge. The ‘I’ type (π-helix) bar is too small to be visible, with only 687 observations.

Figure 3.

Excerpt from a representative query. The query form defines a search for three-residue motifs that do not include Gly, Pro, or prePro residues at position i at 1.5 Å resolution or better. For residue composition, red highlights indicate excluded residues. For flexible-syntax boxes, green highlights indicate valid input, and an example of the flexible query syntax is visible: ‘−180–90,90–180' for ω, describing a search for trans peptides.

Figure 4.

Excerpt from a representative output. The Ramachandran plot shows results of a search for three-residue motifs that do not include Gly, Pro or prePro residues at position i at 1.5 Å resolution or better with other settings left at their defaults. Coloration of the plot in green indicates the observation density in each bin, from low (dark) to high (light). The gray popup box on the left gives information for the pixel over which the cursor is placed. It is one of the most highly populated bins in the α region. The total result count is visible at the left edge of the top navigation bar.