The In Silico Prediction of Hotspot Residues that Contribute to the Structural Stability of Subunit Interfaces of a Picornavirus Capsid

Abstract

The assembly of picornavirus capsids proceeds through the stepwise oligomerization of capsid protein subunits and depends on interactions between critical residues known as hotspots. Few studies have described the identification of hotspot residues at the protein subunit interfaces of the picornavirus capsid, some of which could represent novel drug targets. Using a combination of accessible web servers for hotspot prediction, we performed a comprehensive bioinformatic analysis of the hotspot residues at the intraprotomer, interprotomer and interpentamer interfaces of the Theiler’s murine encephalomyelitis virus (TMEV) capsid. Significantly, many of the predicted hotspot residues were found to be conserved in representative viruses from different genera, suggesting that the molecular determinants of capsid assembly are conserved across the family. The analysis presented here can be applied to any icosahedral structure and provides a platform for in vitro mutagenesis studies to further investigate the significance of these hotspots in critical stages of the virus life cycle with a view to identify potential targets for antiviral drug design.

Genomic Determinants Potentially Associated with Clinical Manifestations of Human-Pathogenic Tick-Borne Flaviviruses

“…There are several bioinformatic predictions of hot spots in genomes which affect different viral properties including cell and tissue tropism [ 47 , 48 , 49 , 50 ]. Some of them are proven in practice.…”

Alpha-Carbonic Anhydrases from Hydrothermal Vent Sources as Potential Carbon Dioxide Sequestration Agents: In Silico Sequence, Structure and Dynamics Analyses

“…The multimeric occurrence of these enzyme complexes, which is brought about by the interaction of residues between monomers, a region termed the interface or the buried surface area (BSA), is often overlooked [43,44]. The BSA contributes to function as well as stability of the protein complex with a group of residues, termed "hotspot residues", contributing significantly to protein stability [45,46]. This study considers their biological assemblies (BAs), revealing the relevance of simulating the CAs in their multimeric states.…”