Scop3D: Three‐dimensional visualization of sequence conservation

Abstract

The integration of a protein's structure with its known sequence variation provides insight on how that protein evolves, for instance in terms of (changing) function or immunogenicity. Yet, collating the corresponding sequence variants into a multiple sequence alignment, calculating each position's conservation, and mapping this information back onto a relevant structure is not straightforward. We therefore built the Sequence Conservation on Protein 3D structure (scop3D) tool to perform these tasks automatically. The output consists of two modified PDB files in which the B-values for each position are replaced by the percentage sequence conservation, or the information entropy for each position, respectively. Furthermore, text files with absolute and relative amino acid occurrences for each position are also provided, along with snapshots of the protein from six distinct directions in space. The visualization provided by scop3D can for instance be used as an aid in vaccine development or to identify antigenic hotspots, which we here demonstrate based on an analysis of the fusion proteins of human respiratory syncytial virus and mumps virus.

Differences in antigenic sites and other functional regions between genotype A and G mumps virus surface proteins

“…The homology model of the F protein was built using PDB-entry 4GIP, which is the F protein of the parainfluenza 5 virus (49% sequence identity). For the mapping of the sequence variation, Scop3D was used 28 , which is a tool designed to map sequence variation onto protein structure. Here, we used this tool to identify differences in residues on positions that are either specific to genotype A or genotype G strains.…”

“…Multiple sequence alignments for the F and HN protein sequences were performed with the aid of Muscle 50 , 51 . The sequence variation was subsequently mapped onto the protein structures with the aid of Scop3D, a tool to visualize variation across multiple sequences on the protein structure 28 . The entropy, which provides information on how random or specific the observed variation is, was also calculated with Scop3D for both proteins.…”

Analysis of Conserved, Computationally Predicted Epitope Regions for VP5 and VP7 Across three Orbiviruses

“…In Scop3D, conservation is the percentage variation at each amino acid position and it gives an idea of the distribution of sequence conservation on a protein structure. 53 Entropy, however, provides information on the random spread of the observed variation across all 20 possible amino acids in each position. 53 Low entropy values therefore indicate that only a few amino acids are possible in a said position, whereas a high entropy value means that many different amino acids are found in a said position.…”

“…Scop3D 53 was used to calculate the sequence variation and entropy of both viral proteins for each individual virus as well as the consensus. Homology models created were used to visualize the sequence conservation and entropy.…”

H9 Influenza Viruses: An Emerging Challenge

“…a All HA positions follow the H9 numbering. Percent of conservation at selected residues is based on the global avian H9N2 HA1 amino acid alignment of 600 sequences from the analysis in Figure 3 with Scop3D entropy calculation (Vermeire et al 2015). (Tse et al 2014).…”