EMERALD-UI: An interactive web application to unveil novel protein biology hidden in the suboptimal-alignment space

TL;DR

EMERALD-UI, an open-source interactive web application which is designed to reveal unexplored biology by visualising stable structural conformations or protein regions hidden in the suboptimal alignment space, is introduced.

Abstract

Life over the past four billion years has been shaped by proteins and their capacity to assemble into three dimensional conformations. Protein sequence alignments have been the enabling technology for exploring the evolution and functional adaptation of proteins across the tree of life. Recent advancements in scaling the prediction of three dimensional protein structures from primary sequence alone, revealed that different modes of conservation and function operate on the sequence and structure level. This difference in protein conservation patterns and their underlying functional change that could emerge in suboptimal alignment configurations is often ignored in optimal protein alignment approaches. We introduce EMERALD-UI, an open-source interactive web application which is designed to reveal unexplored biology by visualising stable structural conformations or protein regions hidden in the suboptimal alignment space. Availability: EMERALD-UI is available at https://algbio.github.io/emerald-ui/. Contact: hdrost001@dundee.ac.uk or alexandru.tomescu@helsinki.fi.

Figures (1)

• Figure 1: Schematic Overview of the EMERALD-UI Workflow. 1) Users can import their protein sequences as FASTA, CIF, PDB, Uniprot and DIAMOND DeepClust clusters for comparisons across the suboptimal alignment space (panel A). 2) Using the protein sequences specified by the user, EMERALD-UI then computes the pairwise (suboptimal) alignments using EMERALD either by relying on the default settings or the users adjusted (or even advanced) settings (panel B) and visualises the corresponding alignment graph which includes all alternative alignment configurations of the suboptimal alignment space (panel C). When lowering the alpha parameter new safety windows across the suboptimal alignment space are revealed. This is captured by paths diverting from the optimal alignment path (blue path). When increasing the delta parameter on the other hand, more alternative alignment paths are revealed. Users can then select an alternative alignment path (red path) for further structural and downstream assessments (panel D). 3) Finally, users can explore which parts of their protein sequence and corresponding structure are alignment safe (stable across suboptimal alignment configurations) (panel F) and forward these proteins to downstream protein annotation databases for further exploration. Alignment available at: https://algbio.github.io/emerald-ui/?seqA=E0CX11&seqB=Q9UDW1