Transmembrane Protein Docking with JabberDock

Abstract

Transmembrane proteins act as an intermediary for a broad range of biological process. Making up 20% to 30% of the proteome, their ubiquitous nature has resulted in them comprising 50% of all targets in drug design. Despite their importance, they make up only 4% of all structures in the PDB database, primarily owing to difficulties associated with isolating and characterizing them. Membrane protein docking algorithms could help to fill this knowledge gap, yet only few exist. Moreover, these existing methods achieve success rates lower than the current best soluble proteins docking software. We present and test a pipeline using our software, JabberDock, to dock membrane proteins. JabberDock docks shapes representative of membrane protein structure and dynamics in their biphasic environment. We verify JabberDock’s ability to yield accurate predictions by applying it to a benchmark of 20 transmembrane dimers, returning a success rate of 75.0%. This makes our software very competitive among available membrane protein–protein docking tools.

New Horizons in Structural Biology of Membrane Proteins: Experimental Evaluation of the Role of Conformational Dynamics and Intrinsic Flexibility

“…JabberDock's defining feature is its usage of a novel protein volumetric representation called spatial and temporal influence density (STID) maps, which are built from short molecular dynamics simulations. Rudden and Deglacomi have presented a pipeline protocol to use this approach for cases involving IMP dimers [193]. They verified JabberDock's ability to yield accurate predictions in a benchmark of 20 transmembrane dimers, returning a success rate of 75.0%.…”

Protein–Protein Docking: Past, Present, and Future

“…The proposed STID maps are proved to be suitable in devising appropriate scoring functions, and it leads to improved performance of the tool. The tool is found to be efficient for transmembrane proteins, too [70].…”

Biobox: a toolbox for biomolecular modelling

“…Our blind protein–protein docking engine, JabberDock ( Rudden and Degiacomi, 2019 ), predicts dimeric arrangements by leveraging a novel molecular representation that encompasses protein electrostatics, shape and local dynamics. JabberDock has been extended to transmembrane protein docking ( Rudden and Degiacomi, 2021 ), and applied to the prediction of the bo 3 oxidase dimeric structure ( Olerinyova et al , 2021 ) by leveraging mass photometry data. Biobox forms the cornerstone of JabberDock by handling the importing and exporting of protein structures and volumetric representations, and manipulating them during the docking process.…”