GrAfSS: a webserver for substructure similarity searching and comparisons in the structures of proteins and RNA

Abstract

The GrAfSS (Graph theoretical Applications for Substructure Searching) webserver is a platform to search for three-dimensional substructures of: (i) amino acid side chains in protein structures; and (ii) base arrangements in RNA structures. The webserver interfaces the functions of five different graph theoretical algorithms – ASSAM, SPRITE, IMAAAGINE, NASSAM and COGNAC – into a single substructure searching suite. Users will be able to identify whether a three-dimensional (3D) arrangement of interest, such as a ligand binding site or 3D motif, observed in a protein or RNA structure can be found in other structures available in the Protein Data Bank (PDB). The webserver also allows users to determine whether a protein or RNA structure of interest contains substructural arrangements that are similar to known motifs or 3D arrangements. These capabilities allow for the functional annotation of new structures that were either experimentally determined or computationally generated (such as the coordinates generated by AlphaFold2) and can provide further insights into the diversity or conservation of functional mechanisms of structures in the PDB. The computed substructural superpositions are visualized using integrated NGL viewers. The GrAfSS server is available at http://mfrlab.org/grafss/.

Understanding structural and functional diversity of ATP-PPases using protein domains and functional families in CATH database

“…In addition, a PBL motif residue D248 2 conserved by all GMPS is also considered part of the structural functional motif. The specificity of the D248, Y370, L414 and F415 structural arrangement (DYLF motif) in bacterial GMPS SDPs was determined by annotating their occurrences in a large set of 3,637 high quality AF2 predicted HUP domains using the Amino acid pattern Search for Substructures and Motifs (ASSAM) webserver 58 . ASSAM matched 54/56 bacterial and Plasmodium FunFam members to the DYLF motif ( Figure.4 ) with no eukaryotic matches.…”

“…The ASSAM algorithm relies on a graph theoretical approach to scan the input motif against structures of protein structure databases 37 , including the CATH database. Databases for HUP structures from the PDB classified by CATH and those predicted by AF2 were generated specifically for this work and have been made available as database options on the Graph theoretical Applications for Substructure Searching (GrAfSS) webserver 58 . ASSAM uses representations of the amino acid side chains as pseudo-atoms to generate vectors, ultimately representing structures as a graph consisting of multiple vectors 37 .…”

Structural and functional analyses of Burkholderia pseudomallei BPSL1038 reveal a Cas-2/VapD nuclease sub-family

“…The BPSL1038, CRISPR-Cas2 associated and VapD proteins used in the sequence and structure analysis and comparison were labelled and listed throughout the manuscript as shown in Supplementary Table 3 . Substructure similarity searching was carried out using the latest version of the ASSAM computer program accessed as a web application 55 , 56 .…”